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1
van Beek, Ellen M., Fiona Cochrane, A. Neil Barclay, and Timo K. van den Berg. "Signal Regulatory Proteins in the Immune System." Journal of Immunology 175, no. 12 (2005): 7781–87. http://dx.doi.org/10.4049/jimmunol.175.12.7781.
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Bouton, C., and J. C. Drapier. "Iron Regulatory Proteins as NO Signal Transducers." Science Signaling 2003, no. 182 (2003): pe17. http://dx.doi.org/10.1126/scisignal.1822003pe17.
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Bouton, C., and J. C. Drapier. "Iron Regulatory Proteins as NO Signal Transducers." Science Signaling 2003, no. 182 (2003): pe17. http://dx.doi.org/10.1126/stke.2003.182.pe17.
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Mesa, S., H. Hennecke, and H. M. Fischer. "A multitude of CRP/FNR-like transcription proteins in Bradyrhizobium japonicum." Biochemical Society Transactions 34, no. 1 (2006): 156–59. http://dx.doi.org/10.1042/bst0340156.
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In Bradyrhizobium japonicum, the nitrogen-fixing soya bean endosymbiont and facultative denitrifier, three CRP (cAMP receptor protein)/FNR (fumarate and nitrate reductase regulatory protein)-type transcription factors [FixK1, FixK2 and NnrR (nitrite and nitric oxide reductase regulator)] have been studied previously in the context of the regulation of nitrogen fixation and denitrification. The gene expression of both fixK1 and nnrR depends on FixK2, which acts as a key distributor of the ‘low-oxygen’ signal perceived by the two-component regulatory system FixLJ. While the targets for FixK1 are not known, NnrR transduces the nitrogen oxide signal to the level of denitrification gene expression. Besides these three regulators, the complete genome sequence of this organism has revealed the existence of 13 additional CRP/FNR-type proteins whose functions have not yet been studied. Based on sequence similarity and phylogenetic analysis, we discuss in this paper the peculiarities of these additional factors.
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Stamm, Stefan. "Regulation of Alternative Splicing by Reversible Protein Phosphorylation." Journal of Biological Chemistry 283, no. 3 (2007): 1223–27. http://dx.doi.org/10.1074/jbc.r700034200.
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The vast majority of human protein-coding genes are subject to alternative splicing, which allows the generation of more than one protein isoform from a single gene. Cells can change alternative splicing patterns in response to a signal, which creates protein variants with different biological properties. The selection of alternative splice sites is governed by the dynamic formation of protein complexes on the processed pre-mRNA. A unique set of these splicing regulatory proteins assembles on different pre-mRNAs, generating a “splicing” or “messenger ribonucleoprotein code” that determines exon recognition. By influencing protein/protein and protein/RNA interactions, reversible protein phosphorylation modulates the assembly of regulatory proteins on pre-mRNA and therefore contributes to the splicing code. Studies of the serine/arginine-rich protein class of regulators identified different kinases and protein phosphatase 1 as the molecules that control reversible phosphorylation, which controls not only splice site selection, but also the localization of serine/arginine-rich proteins and mRNA export. The involvement of protein phosphatase 1 explains why second messengers like cAMP and ceramide that control the activity of this phosphatase influence alternative splicing. The emerging mechanistic links between splicing regulatory proteins and known signal transduction pathways now allow in detail the understanding how cellular signals modulate gene expression by influencing alternative splicing. This knowledge can be applied to human diseases that are caused by the selection of wrong splice sites.
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Bobay, Benjamin G., James A. Hoch та John Cavanagh. "Dynamics and activation in response regulators: the β4-α4 loop". BioMolecular Concepts 3, № 2 (2012): 175–82. http://dx.doi.org/10.1515/bmc-2011-0063.
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AbstractTwo-component signal transduction systems of microbes are a primary means to respond to signals emanating from environmental and metabolic fluctuations as well as to signals coordinating the cell cycle with macromolecular syntheses, among a large variety of other essential roles. Signals are recognized by a sensor domain of a histidine kinase which serves to convert signal binding to an active transmissible phosphoryl group through a signal-induced ATP-dependent autophosphorylation reaction directed to histidine residue. The sensor kinase is specifically mated to a response regulator, to which it transfers the phosphoryl group that activates the response regulator’s function, most commonly gene repression or activation but also interaction with other regulatory proteins. Two-component systems have been genetically amplified to control a wide variety of cellular processes; for example, both Escherichia coli and Pseudomonas aeruginosa have 60 plus confirmed and putative two-component systems. Bacillus subtilis has 30 plus and Nostoc punctiformis over 100. As genetic amplification does not result in changes in the basic structural folds of the catalytic domains of the sensor kinase or response regulators, each sensor kinase must recognize its partner through subtle changes in residues at the interaction surface between the two proteins. Additionally, the response regulator must prepare itself for efficient activation by the phosphorylation event. In this short review, we discuss the contributions of the critical β4-α4 recognition loop in response regulators to their function. In particular, we focus on this region’s microsecond-millisecond timescale dynamics propensities and discuss how these motions play a major role in response regulator recognition and activation.
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Stec, Wojciech J., and Martin P. Zeidler. "Drosophila SOCS Proteins." Journal of Signal Transduction 2011 (December 13, 2011): 1–8. http://dx.doi.org/10.1155/2011/894510.
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The importance of signal transduction cascades such as the EGFR and JAK/STAT pathways for development and homeostasis is highlighted by the high levels of molecular conservation maintained between organisms as evolutionary diverged as fruit flies and humans. This conservation is also mirrored in many of the regulatory mechanisms that control the extent and duration of signalling in vivo. One group of proteins that represent important physiological regulators of both EGFR and JAK/STAT signalling is the members of the SOCS family. Only 3 SOCS-like proteins are encoded by the Drosophila genome, and despite this low complexity, Drosophila SOCS proteins share many similarities to their human homologues. SOCS36E is both a target gene and negative regulator of JAK/STAT signalling while SOCS44A and SOCS36E represent positive and negative regulators of EGFR signalling. Here we review our current understanding of Drosophila SOCS proteins, their roles in vivo, and future approaches to elucidating their functions.
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Filteau, Marie, Guillaume Diss, Francisco Torres-Quiroz, et al. "Systematic identification of signal integration by protein kinase A." Proceedings of the National Academy of Sciences 112, no. 14 (2015): 4501–6. http://dx.doi.org/10.1073/pnas.1409938112.
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Cellular processes and homeostasis control in eukaryotic cells is achieved by the action of regulatory proteins such as protein kinase A (PKA). Although the outbound signals from PKA directed to processes such as metabolism, growth, and aging have been well charted, what regulates this conserved regulator remains to be systematically identified to understand how it coordinates biological processes. Using a yeast PKA reporter assay, we identified genes that influence PKA activity by measuring protein–protein interactions between the regulatory and the two catalytic subunits of the PKA complex in 3,726 yeast genetic-deletion backgrounds grown on two carbon sources. Overall, nearly 500 genes were found to be connected directly or indirectly to PKA regulation, including 80 core regulators, denoting a wide diversity of signals regulating PKA, within and beyond the described upstream linear pathways. PKA regulators span multiple processes, including the antagonistic autophagy and methionine biosynthesis pathways. Our results converge toward mechanisms of PKA posttranslational regulation by lysine acetylation, which is conserved between yeast and humans and that, we show, regulates protein complex formation in mammals and carbohydrate storage and aging in yeast. Taken together, these results show that the extent of PKA input matches with its output, because this kinase receives information from upstream and downstream processes, and highlight how biological processes are interconnected and coordinated by PKA.
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Gopalan, Janani, Linda Wordeman, and John D. Scott. "Kinase-anchoring proteins in ciliary signal transduction." Biochemical Journal 478, no. 8 (2021): 1617–29. http://dx.doi.org/10.1042/bcj20200869.
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Historically, the diffusion of chemical signals through the cell was thought to occur within a cytoplasmic soup bounded by the plasma membrane. This theory was predicated on the notion that all regulatory enzymes are soluble and moved with a Brownian motion. Although enzyme compartmentalization was initially rebuffed by biochemists as a ‘last refuge of a scoundrel', signal relay through macromolecular complexes is now accepted as a fundamental tenet of the burgeoning field of spatial biology. A-Kinase anchoring proteins (AKAPs) are prototypic enzyme-organizing elements that position clusters of regulatory proteins at defined subcellular locations. In parallel, the primary cilium has gained recognition as a subcellular mechanosensory organelle that amplifies second messenger signals pertaining to metazoan development. This article highlights advances in our understanding of AKAP signaling within the primary cilium and how defective ciliary function contributes to an increasing number of diseases known as ciliopathies.
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Martínez-Argudo, Isabel, Paloma Salinas, Rafael Maldonado, and Asunción Contreras. "Domain Interactions on the ntr Signal Transduction Pathway: Two-Hybrid Analysis of Mutant and Truncated Derivatives of Histidine Kinase NtrB." Journal of Bacteriology 184, no. 1 (2002): 200–206. http://dx.doi.org/10.1128/jb.184.1.200-206.2002.
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ABSTRACT We have used the yeast two-hybrid system to analyze protein-protein interactions mediated by domains of regulatory proteins of the ntr signal transduction system, including interactions among NtrB derivatives and their interactions with NtrC and PII from Klebsiella pneumoniae. Interactions took place only between proteins or protein domains belonging to the ntr signal transduction system and not between proteins or domains from noncognate regulators. NtrB and its transmitter domain, but not NtrC, CheA, or the cytoplasmic C terminus of EnvZ, interacted with PII. In addition, interaction of NtrB with NtrC, but not with PII, depended on the histidine phosphotransfer domain. Point mutation A129T, diminishing the NtrC phosphatase activity of NtrB, affected the strength of the signals between NtrC and the transmitter module of NtrB but had no impact on PII signals, suggesting that A129T prevents the conformational change needed by NtrB to function as a phosphatase for NtrC, rather than disturbing binding to PII.
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Liénard, Hélène, Pierre Bruhns, Odile Malbec, Wolf H. Fridman, and Marc Daëron. "Signal Regulatory Proteins Negatively Regulate Immunoreceptor-dependent Cell Activation." Journal of Biological Chemistry 274, no. 45 (1999): 32493–99. http://dx.doi.org/10.1074/jbc.274.45.32493.
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Öbrink, Björn. "CEA adhesion molecules: multifunctional proteins with signal-regulatory properties." Current Opinion in Cell Biology 9, no. 5 (1997): 616–26. http://dx.doi.org/10.1016/s0955-0674(97)80114-7.
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Umemori, Hisashi, and Joshua R. Sanes. "Signal Regulatory Proteins (SIRPS) Are Secreted Presynaptic Organizing Molecules." Journal of Biological Chemistry 283, no. 49 (2008): 34053–61. http://dx.doi.org/10.1074/jbc.m805729200.
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B Whitchurch, Cynthia. "Complexity in ?2-component? signal transduction systems." Microbiology Australia 27, no. 3 (2006): 128. http://dx.doi.org/10.1071/ma06128.
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The ?2-component? regulatory systems of bacteria are the predominant signal transduction mechanisms that bacteria utilise to modulate behaviours and metabolism in response to environmental changes. These systems classically involve two proteins ? a membrane bound sensor histidine kinase and a soluble response regulator.
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Martín-Mora, David, Matilde Fernández, Félix Velando, et al. "Functional Annotation of Bacterial Signal Transduction Systems: Progress and Challenges." International Journal of Molecular Sciences 19, no. 12 (2018): 3755. http://dx.doi.org/10.3390/ijms19123755.
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Bacteria possess a large number of signal transduction systems that sense and respond to different environmental cues. Most frequently these are transcriptional regulators, two-component systems and chemosensory pathways. A major bottleneck in the field of signal transduction is the lack of information on signal molecules that modulate the activity of the large majority of these systems. We review here the progress made in the functional annotation of sensor proteins using high-throughput ligand screening approaches of purified sensor proteins or individual ligand binding domains. In these assays, the alteration in protein thermal stability following ligand binding is monitored using Differential Scanning Fluorimetry. We illustrate on several examples how the identification of the sensor protein ligand has facilitated the elucidation of the molecular mechanism of the regulatory process. We will also discuss the use of virtual ligand screening approaches to identify sensor protein ligands. Both approaches have been successfully applied to functionally annotate a significant number of bacterial sensor proteins but can also be used to study proteins from other kingdoms. The major challenge consists in the study of sensor proteins that do not recognize signal molecules directly, but that are activated by signal molecule-loaded binding proteins.
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Tomasello, Elena, Charles Cant, Hans-Jörg Bühring та ін. "Association of signal-regulatory proteins β with KARAP/DAP-12". European Journal of Immunology 30, № 18 (2000): 2147. http://dx.doi.org/10.1002/1521-4141(2000)30:18<2147::aid-immu2147>3.3.co;2-9.
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Tomasello, Elena, Charles Cant, Hans-Jörg Bühring та ін. "Association of signal-regulatory proteins β with KARAP/DAP-12". European Journal of Immunology 30, № 8 (2000): 2147–56. http://dx.doi.org/10.1002/1521-4141(2000)30:8<2147::aid-immu2147>3.0.co;2-1.
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Shpakov, Alexander O. "Signal Protein-Derived Peptides as Functional Probes and Regulators of Intracellular Signaling." Journal of Amino Acids 2011 (August 23, 2011): 1–25. http://dx.doi.org/10.4061/2011/656051.
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The functionally important regions of signal proteins participating in their specific interaction and responsible for transduction of hormonal signal into cell are rather short in length, having, as a rule, 8 to 20 amino acid residues. Synthetic peptides corresponding to these regions are able to mimic the activated form of full-size signal protein and to trigger signaling cascades in the absence of hormonal stimulus. They modulate protein-protein interaction and influence the activity of signal proteins followed by changes in their regulatory and catalytic sites. The present review is devoted to the achievements and perspectives of the study of signal protein-derived peptides and to their application as selective and effective regulators of hormonal signaling systems in vitro and in vivo. Attention is focused on the structure, biological activity, and molecular mechanisms of action of peptides, derivatives of the receptors, G protein α subunits, and the enzymes generating second messengers.
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Radchenko, Martha, and Mike Merrick. "The role of effector molecules in signal transduction by PII proteins." Biochemical Society Transactions 39, no. 1 (2011): 189–94. http://dx.doi.org/10.1042/bst0390189.
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PII proteins are one of the most widely distributed signal transduction proteins in Nature, being ubiquitous in bacteria, archaea and plants. They act by protein–protein interaction to control the activities of a wide range of enzymes, transcription factors and transport proteins, the great majority of which are involved in cellular nitrogen metabolism. The regulatory activities of PII proteins are mediated through their ability to bind the key effector metabolites 2-OG (2-oxoglutarate), ATP and ADP. However, the molecular basis of these regulatory effects remains unclear. Recent advances in the solution of the crystal structures of PII proteins complexed with some of their target proteins, as well as the identification of the ATP/ADP- and 2-OG-binding sites, have improved our understanding of their mode of action. In all of the complex structures solved to date, the flexible T-loops of PII facilitate interaction with the target protein. The effector molecules appear to play a key role in modulating the conformation of the T-loops and thereby regulating the interactions between PII and its targets.
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Dunny, Gary M., and Ronnie Per-Arne Berntsson. "Enterococcal Sex Pheromones: Evolutionary Pathways to Complex, Two-Signal Systems." Journal of Bacteriology 198, no. 11 (2016): 1556–62. http://dx.doi.org/10.1128/jb.00128-16.
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Gram-positive bacteria carry out intercellular communication using secreted peptides. Important examples of this type of communication are the enterococcal sex pheromone systems, in which the transfer of conjugative plasmids is controlled by intercellular signaling among populations of donors and recipients. This review focuses on the pheromone response system of the conjugative plasmid pCF10. The peptide pheromones regulating pCF10 transfer act by modulating the ability of the PrgX transcription factor to repress the transcription of an operon encoding conjugation functions. Many Gram-positive bacteria regulate important processes, including the production of virulence factors, biofilm formation, sporulation, and genetic exchange using peptide-mediated signaling systems. The key master regulators of these systems comprise the RRNPP (RggRap/NprR/PlcR/PrgX) family of intracellular peptide receptors; these regulators show conserved structures. While many RRNPP systems include a core module of two linked genes encoding the regulatory protein and its cognate signaling peptide, the enterococcal sex pheromone plasmids have evolved to a complex system that also recognizes a second host-encoded signaling peptide. Additional regulatory genes not found in most RRNPP systems also modulate signal production and signal import in the enterococcal pheromone plasmids. This review summarizes several structural studies that cumulatively demonstrate that the ability of three pCF10 regulatory proteins to recognize the same 7-amino-acid pheromone peptide arose by convergent evolution of unrelated proteins from different families. We also focus on the selective pressures and structure/function constraints that have driven the evolution of pCF10 from a simple, single-peptide system resembling current RRNPPs in other bacteria to the current complex inducible plasmid transfer system.
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Palvimo, J. J. "PIAS proteins as regulators of small ubiquitin-related modifier (SUMO) modifications and transcription." Biochemical Society Transactions 35, no. 6 (2007): 1405–8. http://dx.doi.org/10.1042/bst0351405.
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Transcriptional activity of signal-dependent transcription factors, including nuclear receptors, relies on interacting co-regulator proteins, many of which possess protein-modifying activity. SUMOs (small ubiquitin-related modifiers) and their conjugation pathway components act as co-regulator proteins for numerous transcription factors that also are often targets for SUMO modification. PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)] proteins promote SUMOylation in a manner that resembles the action of RING-type ubiquitin E3 ligases. PIAS proteins were initially named for their ability to interact with STAT proteins and inhibit their activity, but their interactions and functions are not restricted to the STATs. Moreover, PIAS proteins do not operate merely as SUMO E3s, since their co-regulator effects are often independent of their RING finger but dependent on their SIM (SUMO-interacting motif) or SAP (scaffold attachment factor-A/B/acinus/PIAS) domain capable of interacting with DNA. The modulator activity imparted by the PIAS/SUMO system involves altered subnuclear targeting and/or assembly of transcription complexes. PIAS proteins may act as platforms that facilitate both removal and recruitment of other regulatory proteins in the transcription complexes.
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Robbins, D. J., E. Zhen, M. Cheng, et al. "Regulation and properties of extracellular signal-regulated protein kinases 1, 2, and 3." Journal of the American Society of Nephrology 4, no. 5 (1993): 1104–10. http://dx.doi.org/10.1681/asn.v451104.
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The extracellular signal-regulated kinases ERK1 and ERK2 are 43- and 41-kd enzymes activated by many extracellular cues. They lie within a protein kinase cascade that is used to achieve many cellular responses. In addition to the wide variety of regulatory contexts in which they are activated, they phosphorylate important regulatory proteins, including receptors, transcription factors, cytoskeletal proteins, and other protein kinases. Thus, the stimulation of this kinase cascade is thought to have a pleiotropic action. ERK1 and ERK2 are controlled by phosphorylation on threonine and tyrosine. To understand the regulatory mechanisms, wild-type and mutant ERKs were expressed in bacteria and phosphorylated with MEK, the enzyme that is upstream of ERKs. Wild-type proteins could be activated 500- to 1,000-fold in vitro by MEK. ERK3, an enzyme of 62 kd and only 50% identical to ERK1 and ERK2 in the catalytic core, was also phosphorylated by MEK in vitro. This suggests that all three of these enzymes are targets of common signaling pathways.
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Brito, Belen, Didier Aldon, Patrick Barberis, Christian Boucher, and Stéphane Genin. "A Signal Transfer System Through Three Compartments Transduces the Plant Cell Contact-Dependent Signal Controlling Ralstonia solanacearum hrp Genes." Molecular Plant-Microbe Interactions® 15, no. 2 (2002): 109–19. http://dx.doi.org/10.1094/mpmi.2002.15.2.109.
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Ralstonia solanacearum hrp genes encode a type III secretion system required for disease development in host plants and for hypersensitive response elicitation on non-hosts. hrp genes are expressed in the presence of plant cells through the HrpB regulator. This activation, which requires physical interaction between the bacteria and the plant cell, is sensed by the outer membrane receptor PrhA. PrhA transduces the plant cell contact-dependent signal through a complex regulatory cascade integrated by the PrhJ, HrpG, and HrpB regulators. In this study, we have identified two genes, named prhI and prhR, that belong to the hrp gene cluster and whose predicted products show homology with extracytoplasmic function sigma factors and transmembrane proteins, respectively. Strains carrying a mutation in prhIR show a delayed pathogenic phenotype toward host plants. PrhIR control the plant cell contact-dependent activation of hrp genes. prhIR gene expression is induced by a signal present in the plant cell co-culture that is not PrhA-dependent. Genetic evidence shows that PrhIR act upstream of PrhJ in the regulatory cascade, likely transducing the signal sensed by PrhA through the periplasm as described for signal transfer systems through three compartments. This is the first report of such a surface signaling mechanism activating pathogenicity determinants in response to a nondiffusible plant cell wall signal.
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Vandergaast, Rianna, Jonathan K. Mitchell, Nathaniel M. Byers, and Paul D. Friesen. "Insect Inhibitor-of-Apoptosis (IAP) Proteins Are Negatively Regulated by Signal-Induced N-Terminal Degrons Absent within Viral IAP Proteins." Journal of Virology 89, no. 8 (2015): 4481–93. http://dx.doi.org/10.1128/jvi.03659-14.
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ABSTRACTInhibitor-of-apoptosis (IAP) proteins are key regulators of the innate antiviral response by virtue of their capacity to respond to signals affecting cell survival. In insects, wherein the host IAP provides a primary restriction to apoptosis, diverse viruses trigger rapid IAP depletion that initiates caspase-mediated apoptosis, thereby limiting virus multiplication. We report here that the N-terminal leader of two insect IAPs,Spodoptera frugiperdaSfIAP andDrosophila melanogasterDIAP1, contain distinct instability motifs that regulate IAP turnover and apoptotic consequences. Functioning as a protein degron, the cellular IAP leader dramatically shortened the life span of a long-lived viral IAP (Op-IAP3) when fused to its N terminus. The SfIAP degron contains mitogen-activated kinase (MAPK)-like regulatory sites, responsible for MAPK inhibitor-sensitive phosphorylation of SfIAP. Hyperphosphorylation correlated with increased SfIAP turnover independent of the E3 ubiquitin-ligase activity of the SfIAP RING, which also regulated IAP stability. Together, our findings suggest that the SfIAP phospho-degron responds rapidly to a signal-activated kinase cascade, which regulates SfIAP levels and thus apoptosis. The N-terminal leader of dipteran DIAP1 also conferred virus-induced IAP depletion by a caspase-independent mechanism. DIAP1 instability mapped to previously unrecognized motifs that are not found in lepidopteran IAPs. Thus, the leaders of cellular IAPs from diverse insects carry unique signal-responsive degrons that control IAP turnover. Rapid response pathways that trigger IAP degradation and initiate apoptosis independent of canonical prodeath gene (Reaper-Grim-Hid) expression may provide important innate immune advantages. Furthermore, the elimination of these response motifs within viral IAPs, including those of baculoviruses, explains their unusual stability and their potent antiapoptotic activity.IMPORTANCEApoptosis is an effective means by which a host controls virus infection. In insects, inhibitor-of-apoptosis (IAP) proteins act as regulatory sentinels by responding to cellular signals that determine the fate of infected cells. We discovered that lepidopteran (moth and butterfly) IAPs, which are degraded upon baculovirus infection, are controlled by a conserved phosphorylation-sensitive degron within the IAP N-terminal leader. The degron likely responds to virus-induced kinase-specific signals for degradation through SKP1/Cullin/F-box complex-mediated ubiquitination. Such signal-induced destruction of cellular IAPs is distinct from degradation caused by well-known IAP antagonists, which act to expel IAP-bound caspases. The major implication of this study is that insects have multiple signal-responsive mechanisms by which the sentinel IAPs are actively degraded to initiate host apoptosis. Such diversity of pathways likely provides insects with rapid and efficient strategies for pathogen control. Furthermore, the absence of analogous degrons in virus-encoded IAPs explains their relative stability and antiapoptotic potency.
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Sugiura, Reiko, Ryosuke Satoh, Shunji Ishiwata, Nanae Umeda, and Ayako Kita. "Role of RNA-Binding Proteins in MAPK Signal Transduction Pathway." Journal of Signal Transduction 2011 (April 5, 2011): 1–8. http://dx.doi.org/10.1155/2011/109746.
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Mitogen-activated protein kinases (MAPKs), which are found in all eukaryotes, are signal transducing enzymes playing a central role in diverse biological processes, such as cell proliferation, sexual differentiation, and apoptosis. The MAPK signaling pathway plays a key role in the regulation of gene expression through the phosphorylation of transcription factors. Recent studies have identified several RNA-binding proteins (RBPs) as regulators of MAPK signaling because these RBPs bind to the mRNAs encoding the components of the MAPK pathway and regulate the stability of their transcripts. Moreover, RBPs also serve as targets of MAPKs because MAPK phosphorylate and regulate the ability of RBPs to bind and stabilize target mRNAs, thus controlling various cellular functions. In this review, we present evidence for the significance of the MAPK signaling in the regulation of RBPs and their target mRNAs, which provides additional information about the regulatory mechanism underlying gene expression. We further present evidence for the clinical importance of the posttranscriptional regulation of mRNA stability and its implications for drug discovery.
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Wang, Qin, and Chentao Lin. "Mechanisms of Cryptochrome-Mediated Photoresponses in Plants." Annual Review of Plant Biology 71, no. 1 (2020): 103–29. http://dx.doi.org/10.1146/annurev-arplant-050718-100300.
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Cryptochromes are blue-light receptors that mediate photoresponses in plants. The genomes of most land plants encode two clades of cryptochromes, CRY1 and CRY2, which mediate distinct and overlapping photoresponses within the same species and between different plant species. Photoresponsive protein–protein interaction is the primary mode of signal transduction of cryptochromes. Cryptochromes exist as physiologically inactive monomers in the dark; the absorption of photons leads to conformational change and cryptochrome homooligomerization, which alters the affinity of cryptochromes interacting with cryptochrome-interacting proteins to form various cryptochrome complexes. These cryptochrome complexes, collectively referred to as the cryptochrome complexome, regulate transcription or stability of photoresponsive proteins to modulate plant growth and development. The activity of cryptochromes is regulated by photooligomerization; dark monomerization; cryptochrome regulatory proteins; and cryptochrome phosphorylation, ubiquitination, and degradation. Most of the more than 30 presently known cryptochrome-interacting proteins are either regulated by other photoreceptors or physically interactingwith the protein complexes of other photoreceptors. Some cryptochrome-interacting proteins are also hormonal signaling or regulatory proteins. These two mechanisms enable cryptochromes to integrate blue-light signals with other internal and external signals to optimize plant growth and development.
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Das, Tanuza, Eun Joo Song, and Eunice EunKyeong Kim. "The Multifaceted Roles of USP15 in Signal Transduction." International Journal of Molecular Sciences 22, no. 9 (2021): 4728. http://dx.doi.org/10.3390/ijms22094728.
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Ubiquitination and deubiquitination are protein post-translational modification processes that have been recognized as crucial mediators of many complex cellular networks, including maintaining ubiquitin homeostasis, controlling protein stability, and regulating several signaling pathways. Therefore, some of the enzymes involved in ubiquitination and deubiquitination, particularly E3 ligases and deubiquitinases, have attracted attention for drug discovery. Here, we review recent findings on USP15, one of the deubiquitinases, which regulates diverse signaling pathways by deubiquitinating vital target proteins. Even though several basic previous studies have uncovered the versatile roles of USP15 in different signaling networks, those have not yet been systematically and specifically reviewed, which can provide important information about possible disease markers and clinical applications. This review will provide a comprehensive overview of our current understanding of the regulatory mechanisms of USP15 on different signaling pathways for which dynamic reverse ubiquitination is a key regulator.
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Arcondéguy, Tania, Rachael Jack, and Mike Merrick. "PII Signal Transduction Proteins, Pivotal Players in Microbial Nitrogen Control." Microbiology and Molecular Biology Reviews 65, no. 1 (2001): 80–105. http://dx.doi.org/10.1128/mmbr.65.1.80-105.2001.
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SUMMARY The PII family of signal transduction proteins are among the most widely distributed signal proteins in the bacterial world. First identified in 1969 as a component of the glutamine synthetase regulatory apparatus, PII proteins have since been recognized as playing a pivotal role in control of prokaryotic nitrogen metabolism. More recently, members of the family have been found in higher plants, where they also potentially play a role in nitrogen control. The PII proteins can function in the regulation of both gene transcription, by modulating the activity of regulatory proteins, and the catalytic activity of enzymes involved in nitrogen metabolism. There is also emerging evidence that they may regulate the activity of proteins required for transport of nitrogen compounds into the cell. In this review we discuss the history of the PII proteins, their structures and biochemistry, and their distribution and functions in prokaryotes. We survey data emerging from bacterial genome sequences and consider other likely or potential targets for control by PII proteins.
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Rogov, Vladimir V., Kerstin Schmöe, Fank Löhr, Natalia Yu Rogova, Frank Bernhard, and Volker Dötsch. "Modulation of the Rcs-mediated signal transfer by conformational flexibility." Biochemical Society Transactions 36, no. 6 (2008): 1427–32. http://dx.doi.org/10.1042/bst0361427.
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The Rcs (regulator of capsule synthesis) signalling complex comprises the membrane-associated hybrid sensor kinases RcsC and RcsD, the transcriptional regulator RcsB and the two co-inducers RcsA and RcsF. Acting as a global regulatory network, the Rcs phosphorelay controls multiple cellular pathways including capsule synthesis, cell division, motility, biofilm formation and virulence mechanisms. Signal-dependent communication of the individual Rcs domains showing histidine kinase, phosphoreceiver, phosphoryl transfer and DNA-binding activities is characteristic and essential for the modulation of signal transfer. We have analysed the structures of core elements of the Rcs network including the RcsC-PR (phosphoreceiver domain of RcsC) and the RcsD-HPt (histidine phosphotransfer domain of RcsD), and we have started to characterize the dynamics and recognition mechanisms of the proteins. RcsC-PR represents a typical CheY-like α/β/α sandwich fold and it shows a large conformational flexibility near the active-site residue Asp875. NMR analysis revealed that RcsC-PR is able to adopt preferred conformations upon Mg2+ co-ordination, BeF3− activation, phosphate binding and RcsD-HPt recognition. In contrast, the α-helical structure of RcsD-HPt is conformationally stable and contains a recognition area in close vicinity to the active-site His842 residue. Our studies indicate the importance of protein dynamics and conformational exchange for the differential response to the variety of signals perceived by complex regulatory networks.
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Baker, Anna W., Kenneth A. Satyshur, Neydis Moreno Morales, and Katrina T. Forest. "Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction." Journal of Bacteriology 198, no. 8 (2016): 1218–29. http://dx.doi.org/10.1128/jb.00872-15.
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ABSTRACTBacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRRmon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems.IMPORTANCEBphP histidine kinases and their cognate response regulators comprise widespread red light-sensing two-component systems. Much work on BphPs has focused on structural understanding of light sensing and on enhancing the natural infrared fluorescence of these proteins, rather than on signal transduction or the resultant phenotypes. To begin to address this knowledge gap, we solved the crystal structures of two single-domain response regulators encoded by a region immediately downstream of that encoding BphPs. We observed a previously unknown arm-in-arm dimer linkage. Monomerization via deletion of the C-terminal dimerization motif had an inhibitory effect on net response regulator phosphorylation, underlining the importance of these unusual dimers for signal transduction.
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Koksharova, Olga A., Ivan O. Butenko, Olga V. Pobeguts, Nina A. Safronova та Vadim M. Govorun. "Proteomic Insights into Starvation of Nitrogen-Replete Cells of Nostoc sp. PCC 7120 under β-N-Methylamino-L-Alanine (BMAA) Treatment". Toxins 12, № 6 (2020): 372. http://dx.doi.org/10.3390/toxins12060372.
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All cyanobacteria produce a neurotoxic non-protein amino acid β-N-methylamino-L-alanine (BMAA). However, the biological function of BMAA in the regulation of cyanobacteria metabolism still remains undetermined. It is known that BMAA suppresses the formation of heterocysts in diazotrophic cyanobacteria under nitrogen starvation conditions, and BMAA induces the formation of heterocyst-like cells under nitrogen excess conditions, by causing the expression of heterocyst-specific genes that are usually “silent” under nitrogen-replete conditions, as if these bacteria receive a nitrogen deficiency intracellular molecular signal. In order to find out the molecular mechanisms underlying this unexpected BMAA effect, we studied the proteome of cyanobacterium Nostoc sp. PCC 7120 grown under BMAA treatment in nitrogen-replete medium. Experiments were performed in two experimental settings: (1) in control samples consisted of cells grown without the BMAA treatment and (2) the treated samples consisted of cells grown with addition of an aqueous solution of BMAA (20 µM). In total, 1567 different proteins of Nostoc sp. PCC 7120 were identified by LC-MS/MS spectrometry. Among them, 80 proteins belonging to different functional categories were chosen for further functional analysis and interpretation of obtained proteomic data. Here, we provide the evidence that a pleiotropic regulatory effect of BMAA on the proteome of cyanobacterium was largely different under conditions of nitrogen-excess compared to its effect under nitrogen starvation conditions (that was studied in our previous work). The most significant difference in proteome expression between the BMAA-treated and untreated samples under different growth conditions was detected in key regulatory protein PII (GlnB). BMAA downregulates protein PII in nitrogen-starved cells and upregulates this protein in nitrogen-replete conditions. PII protein is a key signal transduction protein and the change in its regulation leads to the change of many other regulatory proteins, including different transcriptional factors, enzymes and transporters. Complex changes in key metabolic and regulatory proteins (RbcL, RbcS, Rca, CmpA, GltS, NodM, thioredoxin 1, RpbD, ClpP, MinD, RecA, etc.), detected in this experimental study, could be a reason for the appearance of the “starvation” state in nitrogen-replete conditions in the presence of BMAA. In addition, 15 proteins identified in this study are encoded by genes, which are under the control of NtcA—a global transcriptional regulator—one of the main protein partners and transcriptional regulators of PII protein. Thereby, this proteomic study gives a possible explanation of cyanobacterium starvation under nitrogen-replete conditions and BMAA treatment. It allows to take a closer look at the regulation of cyanobacteria metabolism affected by this cyanotoxin.
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Deponte, Marcel, and Christopher Horst Lillig. "Enzymatic control of cysteinyl thiol switches in proteins." Biological Chemistry 396, no. 5 (2015): 401–13. http://dx.doi.org/10.1515/hsz-2014-0280.
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Abstract The spatiotemporal modification of specific cysteinyl residues in proteins has emerged as a novel concept in signal transduction. Such modifications alter the redox state of the cysteinyl thiol group, with implications for the structure and biological function of the protein. Regulatory cysteines are therefore classified as ‘thiol switches’. In this review we emphasize the relevance of enzymes for specific and efficient redox sensing, evaluate prerequisites and general properties of redox switches, and highlight mechanistic principles for toggling thiol switches. Moreover, we provide an overview of potential mechanisms for the initial formation of regulatory disulfide bonds. In brief, we address the three basic questions (i) what defines a thiol switch, (ii) which parameters confer signal specificity, and (iii) how are thiol switches oxidized?
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PANEBRA, A., and S. KHURANA. "Actin regulatory proteins as signal transducers: The microvillar actin binding protein villin." Gastroenterology 120, no. 5 (2001): A698. http://dx.doi.org/10.1016/s0016-5085(01)83474-0.
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Panebra, Alfredo, and Seema Khurana. "Actin regulatory proteins as signal transducers: The microvillar actin binding protein villin." Gastroenterology 120, no. 5 (2001): A698. http://dx.doi.org/10.1016/s0016-5085(08)83474-9.
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Katzenberger, Rebeccah J., Matthew S. Marengo, and David A. Wassarman. "Control of Alternative Splicing by Signal-dependent Degradation of Splicing-regulatory Proteins." Journal of Biological Chemistry 284, no. 16 (2009): 10737–46. http://dx.doi.org/10.1074/jbc.m809506200.
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Milanesi, Riccardo, Paola Coccetti, and Farida Tripodi. "The Regulatory Role of Key Metabolites in the Control of Cell Signaling." Biomolecules 10, no. 6 (2020): 862. http://dx.doi.org/10.3390/biom10060862.
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Robust biological systems are able to adapt to internal and environmental perturbations. This is ensured by a thick crosstalk between metabolism and signal transduction pathways, through which cell cycle progression, cell metabolism and growth are coordinated. Although several reports describe the control of cell signaling on metabolism (mainly through transcriptional regulation and post-translational modifications), much fewer information is available on the role of metabolism in the regulation of signal transduction. Protein-metabolite interactions (PMIs) result in the modification of the protein activity due to a conformational change associated with the binding of a small molecule. An increasing amount of evidences highlight the role of metabolites of the central metabolism in the control of the activity of key signaling proteins in different eukaryotic systems. Here we review the known PMIs between primary metabolites and proteins, through which metabolism affects signal transduction pathways controlled by the conserved kinases Snf1/AMPK, Ras/PKA and TORC1. Interestingly, PMIs influence also the mitochondrial retrograde response (RTG) and calcium signaling, clearly demonstrating that the range of this phenomenon is not limited to signaling pathways related to metabolism.
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Jethmalani, Yogita, and Erin M. Green. "Using Yeast to Define the Regulatory Role of Protein Lysine Methylation." Current Protein & Peptide Science 21, no. 7 (2020): 690–98. http://dx.doi.org/10.2174/1389203720666191023150727.
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The post-translational modifications (PTM) of proteins are crucial for cells to survive under diverse environmental conditions and to respond to stimuli. PTMs are known to govern a broad array of cellular processes including signal transduction and chromatin regulation. The PTM lysine methylation has been extensively studied within the context of chromatin and the epigenetic regulation of the genome. However, it has also emerged as a critical regulator of non-histone proteins important for signal transduction pathways. While the number of known non-histone protein methylation events is increasing, the molecular functions of many of these modifications are not yet known. Proteomic studies of the model system Saccharomyces cerevisiae suggest lysine methylation may regulate a diversity of pathways including transcription, RNA processing, translation, and signal transduction cascades. However, there has still been relatively little investigation of lysine methylation as a broad cellular regulator beyond chromatin and transcription. Here, we outline our current state of understanding of non-histone protein methylation in yeast and propose ways in which the yeast system can be leveraged to develop a much more complete picture of molecular mechanisms through which lysine methylation regulates cellular functions.
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Bihn, Elizabeth A., and Robert J. Ferl. "Subcellular Localization of 14-3-3 Regulatory Proteins in Arabidopsis thaliana." HortScience 31, no. 4 (1996): 614e—614. http://dx.doi.org/10.21273/hortsci.31.4.614e.
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The 14-3-3 proteins were originally characterized in mammalian brains and were thought to be specifically involved in neurotransmitter production. Subsequent research has revealed that this family of proteins is ubiquitous in eucaryotic cells and is involved in a wide range of regulatory and signal transduction pathways. For instance, some 14-3-3 proteins have been associated with the signal transduction in response to fungal pathogen attack and to other environmental factors that affect transcription. In Arabidopsis, 10 isoforms of 14-3-3 have been isolated, raising the possibility that diversity of function may be governed by cellular and subcellular specificities of expression and localization. We have investigated the localization of certain 14-3-3 isoforms through transgenic expression of epitope-tagged 14-3-3s.
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Ferraris, R. P., W. W. Kwan, and J. Diamond. "Regulatory signals for intestinal amino acid transporters and peptidases." American Journal of Physiology-Gastrointestinal and Liver Physiology 255, no. 2 (1988): G151—G157. http://dx.doi.org/10.1152/ajpgi.1988.255.2.g151.
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Dietary protein ultimately regulates many processes involved in protein digestion, but it is often unclear whether proteins themselves, peptides, or amino acids (AAs) are the proximate regulatory signal. Hence we compared several processes involved in protein digestion in mice adapted to one of three rations, identical except for containing 54% of either casein, a partial hydrolysate of casein, or a free AA mixture simulating a complete hydrolysate of casein. We measured brush-border uptakes of seven AAs that variously serve as substrates for four AA transporters, and brush-border and cytosolic activities of four peptidases. The three rations yielded essentially the same AA uptake rates. Peptidase activities tended to be lower on the AA ration than on the protein ration. In other studies, all three rations yielded the same rates of brush-border peptide uptake; protein is only modestly more effective than AAs at inducing synthesis of pancreatic proteases; and, depending on the animal species, protein is either much less or much more effective than AAs at stimulating release of cholecystokinin and hence of pancreatic enzymes. Thus the regulators of each process involved in protein digestion are not necessarily that process's substrate. We call attention to other cases in which the functional significance of regulatory signals remains to be understood.
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O'Connell, Aileen, Shi-Qi An, Yvonne McCarthy, et al. "Proteomics Analysis of the Regulatory Role of Rpf/DSF Cell-to-Cell Signaling System in the Virulence of Xanthomonas campestris." Molecular Plant-Microbe Interactions® 26, no. 10 (2013): 1131–37. http://dx.doi.org/10.1094/mpmi-05-13-0155-r.
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The black rot pathogen Xanthomonas campestris utilizes molecules of the diffusible signal factor (DSF) family as signals to regulate diverse processes contributing to virulence. DSF signal synthesis and transduction requires proteins encoded by the rpf gene cluster. RpfF catalyzes DSF synthesis, whereas the RpfCG two-component system links the perception of DSF to alteration in the level of the second messenger cyclic di-GMP. As this nucleotide can exert a regulatory influence at the post-transcriptional and post-translational levels, we have used comparative proteomics to identify Rpf-regulated processes in X. campestris that may not be revealed by transcriptomics. The abundance of a number of proteins was altered in rpfF, rpfC, or rpfG mutants compared with the wild type. These proteins belonged to several functional categories, including biosynthesis and intermediary metabolism, regulation, oxidative stress or antibiotic resistance, and DNA replication. For many of these proteins, the alteration in abundance was not associated with alteration in transcript level. A directed mutational analysis allowed us to describe a number of new virulence factors among these proteins, including elongation factor P and a putative outer membrane protein, which are both widely conserved in bacteria.
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Lee, Vincent T., Sarkis K. Mazmanian, and Olaf Schneewind. "A Program of Yersinia enterocoliticaType III Secretion Reactions Is Activated by Specific Signals." Journal of Bacteriology 183, no. 17 (2001): 4970–78. http://dx.doi.org/10.1128/jb.183.17.4970-4978.2001.
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ABSTRACT Successful establishment of Yersinia infections requires the type III machinery, a protein transporter that injects virulence factors (Yops) into macrophages. It is reported here that theYersinia type III pathway responds to environmental signals by transporting proteins to distinct locations. Yersinia enterocolitica cells sense an increase in extracellular amino acids (glutamate, glutamine, aspartate, and asparagine) that results in the activation of the type III pathway. Another signal, provided by serum proteins such as albumin, triggers the secretion of YopD into the extracellular medium. The third signal, a decrease in calcium concentration, appears to be provided by host cells and causesY. enterocolitica to transport YopE and presumably other virulence factors across the eukaryotic plasma membrane. Mutations in several genes encoding regulatory molecules (lcrG,lcrH, tyeA, yopD,yopN, yscM1, andyscM2) bypass the signal requirement of the type III pathway. Together these results suggest that yersiniae may have evolved distinct secretion reactions in response to environmental signals.
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Bardwell, L. "Mechanisms of MAPK signalling specificity." Biochemical Society Transactions 34, no. 5 (2006): 837–41. http://dx.doi.org/10.1042/bst0340837.
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MAPK (mitogen-activated protein kinase) signalling pathways contribute to the regulation of diverse responses, including normal and pathological aspects of cell growth, division, differentiation and death. Their ubiquity and versatility raise the issue of how they achieve specific coupling of signal with cellular response. How do the kinases in the cascade distinguish their correct substrates from the vast excess of incorrect substrates? Furthermore, how do different signals elicit distinct responses when they are transmitted by the same components? This short review highlights several mechanisms that can promote specificity in MAPK signalling, including tethering interactions between MAPKs and their substrates and regulators mediated by docking sites, feedback loops and cross-pathway regulatory circuits, and the selective activation of scaffold proteins.
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Janiak-Spens, Fabiola, Jeffrey M. Sparling, Michael Gurfinkel, and Ann H. West. "Differential Stabilities of Phosphorylated Response Regulator Domains Reflect Functional Roles of the Yeast Osmoregulatory SLN1 and SSK1 Proteins." Journal of Bacteriology 181, no. 2 (1999): 411–17. http://dx.doi.org/10.1128/jb.181.2.411-417.1999.
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ABSTRACT Osmoregulation in Saccharomyces cerevisiae involves a multistep phosphorelay system requiring three proteins, SLN1, YPD1, and SSK1, that are related to bacterial two-component signaling proteins, in particular, those involved in regulating sporulation inBacillus subtilis and anaerobic respiration inEscherichia coli. The SLN1-YPD1-SSK1 phosphorelay regulates a downstream mitogen-activated protein kinase cascade which ultimately controls the concentration of glycerol within the cell under hyperosmotic stress conditions. The C-terminal response regulator domains of SLN1 and SSK1 and full-length YPD1 have been overexpressed and purified from E. coli. A heterologous system consisting of acetyl phosphate, the bacterial chemotaxis response regulator CheY, and YPD1 has been developed as an efficient means of phosphorylating SLN1 and SSK1 in vitro. The homologous regulatory domains of SLN1 and SSK1 exhibit remarkably different phosphorylated half-lives, a finding that provides insight into the distinct roles that these phosphorylation-dependent regulatory domains play in the yeast osmosensory signal transduction pathway.
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Nakaoka, Yoshikazu, and Issei Komuro. "Gab Docking Proteins in Cardiovascular Disease, Cancer, and Inflammation." International Journal of Inflammation 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/141068.
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The docking proteins of the Grb2-associated binder (Gab) family have emerged as crucial signaling compartments in metazoans. In mammals, the Gab proteins, consisting of Gab1, Gab2, and Gab3, are involved in the amplification and integration of signal transduction evoked by a variety of extracellular stimuli, including growth factors, cytokines, antigens, and other molecules. Gab proteins lack the enzymatic activity themselves; however, when phosphorylated on tyrosine residues, they provide binding sites for multiple Src homology-2 (SH2) domain-containing proteins, such as SH2-containing protein tyrosine phosphatase 2 (SHP2), phosphatidylinositol 3-kinase regulatory subunit p85, phospholipase Cγ, Crk, and GC-GAP. Through these interactions, the Gab proteins transduce signals from activated receptors into pathways with distinct biological functions, thereby contributing to signal diversification. They are known to play crucial roles in numerous physiological processes through their associations with SHP2 and p85. In addition, abnormal Gab protein signaling has been linked to human diseases including cancer, cardiovascular disease, and inflammatory disorders. In this paper, we provide an overview of the structure, effector functions, and regulation of the Gab docking proteins, with a special focus on their associations with cardiovascular disease, cancer, and inflammation.
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Hood, J. K., W. W. Hwang, and P. A. Silver. "The Saccharomyces cerevisiae cyclin Clb2p is targeted to multiple subcellular locations by cis- and trans-acting determinants." Journal of Cell Science 114, no. 3 (2001): 589–97. http://dx.doi.org/10.1242/jcs.114.3.589.
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The cyclin-dependent kinase Cdc28p associates with the cyclin Clb2p to induce mitosis in the yeast Saccharomyces cerevisiae. Several cell cycle regulatory proteins have been shown to require specific nuclear transport events to exert their regulatory functions. Therefore, we investigated the subcellular localization of wild-type Clb2p and several mutant versions of the protein using green fluorescent protein (GFP) fusion constructs. Wild-type Clb2p is primarily nuclear at all points of the cell. A point mutation in a potential leucine-rich nuclear export signal (NES) enhances the nuclear localization of the protein, and delta-yrb2 cells exhibit an apparent Clb2p nuclear export defect. Clb2p contains a bipartite nuclear localization signal (NLS), and its nuclear localization requires the alpha and beta importins (Srp1p and Kap95p), as well as the yeast Ran GTPase and its regulators. Deletion of the Clb2p NLS causes increased cytoplasmic localization of the protein, as well as accumulation at the bud neck. These data indicate that Clb2p exists in multiple places in the yeast cell, possibly allowing Cdc28p to locally phosphorylate substrates at distinct subcellular sites.
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Garcia-Sainz, JA. "Cell Responsiveness and Protein Kinase C: Receptors, G Proteins, and Membrane Effectors." Physiology 6, no. 4 (1991): 169–73. http://dx.doi.org/10.1152/physiologyonline.1991.6.4.169.
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Protein kinase C (PKC) is activated physiologically by the second messenger diacylglycerol and pharmacologically by phorbol esters. This enzyme participates in regulatory feedback loops and in cross-talk between different signal transduction systems. Among PKC substrates are receptors, G proteins, and membrane effectors.
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Isono, Kyoichi, Kazumi Nemoto, Yuanyuan Li, et al. "Overlapping Roles for Homeodomain-Interacting Protein Kinases Hipk1 and Hipk2 in the Mediation of Cell Growth in Response to Morphogenetic and Genotoxic Signals." Molecular and Cellular Biology 26, no. 7 (2006): 2758–71. http://dx.doi.org/10.1128/mcb.26.7.2758-2771.2006.
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ABSTRACT Homeodomain-interacting protein kinase 1 (Hipk1), 2, and 3 genes encode evolutionarily conserved nuclear serine/threonine kinases, which were originally identified as interacting with homeodomain-containing proteins. Hipks have been repeatedly identified as interactors for a vast range of functional proteins, including not only transcriptional regulators and chromatin modifiers but also cytoplasmic signal transducers, transmembrane proteins, and the E2 component of SUMO ligase. Gain-of-function experiments using cultured cells indicate growth regulatory roles for Hipks on receipt of morphogenetic and genotoxic signals. However, Hipk1 and Hipk2 singly deficient mice were grossly normal, and this is expected to be due to a functional redundancy between Hipk1 and Hipk2. Therefore, we addressed the physiological roles of Hipk family proteins by using Hipk1 Hipk2 double mutants. Hipk1 Hipk2 double homozygotes are progressively lost between 9.5 and 12.5 days postcoitus and frequently fail to close the anterior neuropore and exhibit exencephaly. This is most likely due to defective proliferation in the neural fold and underlying paraxial mesoderm, particularly in the ventral region, which may be attributed to decreased responsiveness to Sonic hedgehog signals. The present study indicated the overlapping roles for Hipk1 and Hipk2 in mediating cell proliferation and apoptosis in response to morphogenetic and genotoxic signals during mouse development.
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Mooibroek, Marilyn J., and Jerry H. Wang. "Integration of signal-transduction processes." Biochemistry and Cell Biology 66, no. 6 (1988): 557–66. http://dx.doi.org/10.1139/o88-066.
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The adenylate cyclase – cAMP, phospholipase C – IP3 (inositol 1,4,5-triphosphate), and DAG (diacylglycerol) signal transduction systems are used to illustrate general principles underlying the process of information transfer during cell stimulation. Both systems consist of reaction cascades that convert the external signal to an intracellular messenger, translate the messenger to regulatory activities, and then modulate the activities of appropriate cellular proteins to result in specific cell responses. Almost all of these reactions are under second-messenger-dependent regulation, with many being regulated by multiple messengers. Such complex regulation provides ample opportunities for the fine-tuning of the signal cascades and for coordination between cascades during cell stimulation. Specific examples are used to illustrate how the cell uses different intrasystem and intersystem regulatory reactions to achieve specific responses.
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Martínez-Argudo, Isabel, and Asunción Contreras. "PII T-Loop Mutations Affecting Signal Transduction to NtrB Also Abolish Yeast Two-Hybrid Interactions." Journal of Bacteriology 184, no. 13 (2002): 3746–48. http://dx.doi.org/10.1128/jb.184.13.3746-3748.2002.
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ABSTRACT Mutations A49P and Δ47-53 at the T loop of the Escherichia coli GlnB (PII) protein impair regulatory interactions with the two-component sensor regulator NtrB (P. Jiang, P. Zucker, M. R. Atkinson, E. S. Kamberov, W. Tirasophon, P. Chandran, B. R. Schepke, and A. J. Ninfa, J. Bacteriol. 179: 4342-4353, 1997). We show here that these mutations also impair interactions between PII and NtrB in the yeast two-hybrid system, indicating that defects in NtrB regulation closely reflect binding impairment. The reported results underline the strength of two-hybrid assays for analysis of interactions involving the T loop of PII proteins.
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Liu, Junfeng, Hongyu Zhao, Jun Tan, et al. "Is Subcellular Localization Informative for Modeling Protein-Protein Interaction Signal?" Research Letters in Signal Processing 2008 (2008): 1–5. http://dx.doi.org/10.1155/2008/365152.
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Statistical methods have been intensively applied in genomic signal processing (Dougherty et al. 2005). For budding yeastSaccharomyces cerevisiaewith around 6000 proteins, genome-wide protein-protein-interaction (PPI) (Fromont-Racine et al. 2000, Ito et al. 2001, Newman et al. 2000, and Uetz et al. 2000 among others) and protein subcellular localization (PSL) (Huh et al. 2003) data recently became available and for the latter the presence of 4152 proteins is experimentally tested in each of the 22 subcellular compartments. Recent work shows that multiple biological sources are helpful for both PSL and PPI predictions, and this paper studies statistical feasibility of modeling PPI from PSL since PSLs may play different marginal or joint roles in the complex regulatory network. However, our results indicate that PSL may be controversial for this purpose as an independent source.