共查询到20条相似文献,搜索用时 15 毫秒
1.
Reversible protein phosphorylation catalyzed by kinases and phosphatases is a major form of posttranslational regulation that plays a central role in regulating many signaling pathways. While large families of both protein kinases and protein phosphatases have been identified in plants, kinases outnumber phosphatases. This raises the question of how a relatively limited number of protein phosphatases can maintain protein phosphorylation homeostasis in a cell. Recent studies have shown that Arabidopsis FyPP1 (Phytochrome-associated serine/threonine protein phosphatase 1) and FyPP3 encode the catalytic subunits of protein phosphatase 6 (PP6), and that they directly binds to the A subunits of protein phosphatase 2A (PP2AA proteins), and SAL (SAPS domain-like) proteins to form the heterotrimeric PP6 holoenzyme complex. Emerging evidence is suggesting that PP6, acts in opposition with multiple classes of kinases, to regulate the phosphorylation status of diverse substrates and subsequently numerous developmental processes and responses to environmental stimuli. 相似文献
2.
Rho GTPase-activating proteins in cell regulation 总被引:35,自引:0,他引:35
3.
The nuclear factor-kappaB (NF-kappaB) and c-Jun NH2-terminal kinase (JNK) signaling pathways regulate diverse biological processes, including the immune and inflammatory response, cell growth, apoptosis, and tumour formation. Not surprisingly therefore defects to either pathway contributes to the progression of numerous human disorders. Enhancing our understanding of the mechanisms that control signaling through these pathways is therefore significant as it may enable development of specific treatments. In this regard, CYLD was recently identified as a negative regulator of NF-kappaB and JNK signaling. CYLD has a C-terminal catalytic domain characteristic of deubiquitinating enzymes, and this is essential for CYLD to remove ubiquitin from certain proteins that positively mediate signaling through the NF-kappaB and JNK pathways. Recent studies have revealed a requirement for CYLD in many different processes and have provided some insight into the underlying mechanisms. 相似文献
4.
《Fly》2013,7(6):330-332
The nuclear factor-kappaB (NF-κB) and c-Jun NH2-terminal kinase (JNK) signaling pathways regulate diverse biological processes, including the immune and inflammatory response, cell growth, apoptosis, and tumor formation. Not surprisingly therefore defects to either pathway contribute to the progression of numerous human disorders. Enhancing our understanding of the mechanisms that control signaling through these pathways is therefore significant as it may enable development of specific treatments. In this regard, CYLD was recently identified as a negative regulator of NF-κB and JNK signaling. CYLD has a C-terminal catalytic domain characteristic of deubiquitinating enzymes, and this is essential for CYLD to remove ubiquitin from certain proteins that positively mediate signaling through the NF-κB and JNK pathways. Recent studies have revealed a requirement for CYLD in many different processes and have provided some insight into the underlying mechanisms. 相似文献
5.
PTEN: a tumour suppressor that functions as a phospholipid phosphatase 总被引:22,自引:0,他引:22
The tumour suppressor PTEN has been implicated in a large number of human tumours and is conserved from humans to worms. Characterization of PTEN protein showed that it is a phosphatase that acts on proteins and on 3-phosphorylated phosphoinositides, including phosphatidylinositol (3,4,5)-trisphosphate, and can therefore modulate signal-transduction pathways that involve lipid second messengers. Recent results indicate that at least part of its role is to regulate the activity of the serine/threonine kinase AKT/PKB, and thus influence cell survival signalling. This article discusses the function of PTEN and how this could be linked to its activity as a tumour suppressor. 相似文献
6.
Nuclear localization of CDC25B1 and serine 146 integrity are required for induction of mitosis 总被引:3,自引:0,他引:3
Baldin V Pelpel K Cazales M Cans C Ducommun B 《The Journal of biological chemistry》2002,277(38):35176-35182
CDC25B phosphatases are essential regulators that control cyclin-dependent kinases activities at the entry into mitosis. In this study, we demonstrate that serine 146 is required for two crucial features of CDC25B1. It is essential for CDC25B1 to function as a mitotic inducer and to prevent CDC25B1 export from the nucleus. We also show that serine 146 is phosphorylated in vitro by CDK1-cyclin B. However, phosphorylation of CDC25B does not stimulate its phosphatase activity, and mutation of serine 146 had no effect on its catalytic activity. Serine 146 phosphorylation is proposed to be a key event in the regulation of the CDC25B function in the initiation of mammalian mitosis. 相似文献
7.
Pinning down cell signaling, cancer and Alzheimer's disease 总被引:17,自引:0,他引:17
Lu KP 《Trends in biochemical sciences》2004,29(4):200-209
Protein phosphorylation on certain serine or threonine residues preceding proline (Ser/Thr-Pro) is a pivitol signaling mechanism in diverse cellular processes and its deregulation can lead to human disease. However, little is known about how these phosphorylation events actually control cell signaling. Pin1 is a highly conserved enzyme that isomerizes only the phosphorylated Ser/Thr-Pro bonds in certain proteins, thereby inducing conformational changes. Recent results indicate that such conformational changes following phosphorylation are a novel signaling mechanism pivotal in regulating many cellular functions. This mechanism also offers new insights into the pathogenesis and treatment of human disease, most notably cancer and Alzheimer's disease. Thus, Pin1 plays a key role in linking signal transduction to the pathogenesis of cancer and Alzheimer's disease - two major age-related diseases. 相似文献
8.
Jin Il Lee Sutapa Mukherjee Kyoung–Hye Yoon Meenakshi Dwivedi Jaya Bandyopadhyay 《Journal of biosciences》2013,38(2):417-431
Calcineurin, a well-conserved protein phosphatase 2B (PP2B), is a Ca2+-calmodulin–dependent serine/threonine protein phosphatase that is known to be involved in a myriad of cellular processes and signal transduction pathways. The biological role of calcineurin has been extensively studied in diverse groups of organisms. Homologues of mammalian and Drosophila calcineurin subunits exist in the nematode, Caenorhabditis elegans. The C. elegans counterpart of the catalytic subunit, calcineurin A, cna-1/tax-6, and the regulatory subunit, calcineurin B, cnb-1, are known to express ubiquitously in multiple tissues including neurons. The characterization of C. elegans calcineurin mutants facilitates identification of its physiological functions and signaling pathways. Genetic interactions between cna-1/tax-6 and cnb-1 mutants with a number of mutants involved in several signaling pathways have exemplified the pivotal role of calcineurin in regulating nematode development, behaviour and lifespan (aging). The present review has been aimed to provide a succinct summary of the multiple functions of calcineurin in C. elegans relating to its development, fertility, proliferation, behaviour and lifespan. Analyses of cna-1/tax-6 and cnb-1 interacting proteins and regulators of the phosphatase in this fascinating worm model have an immense scope to identify potential drug targets in various parasitic nematodes, which cause many diseases inflicting huge economic loss; and also for many human diseases, particularly neurodegenerative and myocardial diseases. 相似文献
9.
Vasudevan SA Skoko J Wang K Burlingame SM Patel PN Lazo JS Nuchtern JG Yang J 《Biochemical and biophysical research communications》2005,330(2):511-518
Intracellular signaling pathways and their relationship to malignant progression have become a major focus of cancer biology. The dual-specificity phosphatase (DSP) family is a more recently identified family of intracellular signaling modulators. We have identified a novel protein phosphatase with a well-conserved DSP catalytic domain containing the DSP catalytic motif, xHCxxGxSRS, and mitogen-activated protein kinase phosphatase (MKP) motif, AYLM. Because of these unique characteristics, the protein was named mitogen-activated protein kinase phosphatase-8 (MKP-8). This protein is approximately 20kDa in size and mainly localizes to the nuclear compartment of the cell. MKP-8 is expressed in embryonal cancers (retinoblastoma, neuroepithelioma, and neuroblastoma) and has limited expression in normal tissues. MKP-8 displays significant phosphatase activity that is inhibited by a cysteine to serine substitution in the catalytic domain. When co-expressed with activated MAPKs, MKP-8 is able to inhibit p38 kinase phosphorylation and downstream activity. 相似文献
10.
Protein phosphatase 4 regulates apoptosis, proliferation and mutation rate of human cells 总被引:1,自引:0,他引:1
The proteins which regulate apoptosis are of great importance both in normal cell biological processes and in the development of pathology in the diverse diseases which involve apoptosis dysfunction. The activity of many of these proteins is controlled by reversible phosphorylation, so that the relevant kinases and phosphatases play crucial roles in apoptosis control. Here we report the analysis of the role of the serine/threonine protein phosphatase, protein phosphatase 4, in controlling the apoptosis of HEK 293 T cells, using the complementary techniques of gene over-expression and down regulation through RNA interference. This analysis has demonstrated that PP4 regulates both apoptosis and proliferation in human cells and has also shown that the level of PP4 has a strong influence on gene mutation rate, which is crucial to oncogenesis. A parallel proteomic analysis has shown that the phosphorylation status of many relevant protein targets is affected by changes in PP4 and has focused attention particularly on the critical apoptosis regulators Bad and PEA-15. The phosphorylation of both of these proteins is increased when PP4 levels are suppressed, and is reduced when PP4 levels are increased, with striking consequences for the fate of the cell. 相似文献
11.
Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation 总被引:6,自引:0,他引:6
Oxidative stress has been indicated in a variety of pathological processes such as atherosclerosis, diabetes, and neurodegenerative diseases. Understanding how intracellular signaling pathways respond to oxidative insults such as hydrogen peroxide (H(2)O(2)) would have significant therapeutic implications. Recent genetic studies have placed apoptosis signal-regulating kinase 1 (ASK1) in a pivotal position in transmitting H(2)O(2)-initiated signals. How ASK1 is activated by H(2)O(2), though, remains a subject of intense investigation. Here we report a mechanism by which H(2)O(2) induces ASK1 activation through dynamic control of its phosphorylation at serine 967. We found that treatment of COS7 cells with H(2)O(2) triggers dephosphorylation of Ser-967 through an okadaic acid-sensitive phosphatase, resulting in dissociation of the ASK1.14-3-3 complex with concomitant increase of ASK1 catalytic activity and ASK1-mediated activation of JNK and p38 pathways. 相似文献
12.
Stamm S 《The Journal of biological chemistry》2008,283(3):1223-1227
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. 相似文献
13.
14.
Protein phosphatase 2A: a panoply of enzymes 总被引:1,自引:0,他引:1
Virshup DM 《Current opinion in cell biology》2000,12(2):180-185
Protein phosphatase 2A describes an extended family of intracellular protein serine/threonine phosphatases sharing a common catalytic subunit that regulates a variety of processes by means of diverse regulatory subunits. During the past year, studies have shown that protein phosphatase 2A influences events ranging from the initiation of DNA replication to vertebrate axis formation to apoptosis. 相似文献
15.
Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis 总被引:4,自引:0,他引:4
Embryonic morphogenesis requires the execution of complex mechanisms that regulate the local behaviour of groups of cells. The orchestration of such mechanisms has been mainly deciphered through the identification of conserved families of signalling pathways that spatially and temporally control cell behaviour. However, how this information is processed to control cell shape and cell dynamics is an open area of investigation. The framework that emerges from diverse disciplines such as cell biology, physics and developmental biology points to adhesion and cortical actin networks as regulators of cell surface mechanics. In this context, a range of developmental phenomena can be explained by the regulation of cell surface tension. 相似文献
16.
17.
New insights into TGF-beta-Smad signalling 总被引:1,自引:0,他引:1
18.
PP2A: unveiling a reluctant tumor suppressor 总被引:2,自引:0,他引:2
Although evidence has suggested that the serine/threonine protein phosphatase 2A (PP2A) might be a tumor suppressor protein, it has been difficult to pin down its role in tumor suppression because it acts in a wide variety of signaling pathways. Recent findings, including work in this issue by Junttila et al. (2007), provide convincing evidence that suppression of PP2A activity cooperates with other oncogenic changes to cause transformation of multiple cell types. 相似文献
19.
20.
RAC/ROP GTPases are a family of plant-specific signaling molecules solely representing the Ras and Rho family of Ras-related G proteins in plants. RAC/ROPs potentially interact with cell surface-associated signal perception apparatus for a broad range of extracellular stimuli, including hormones, pathogen elicitors and abiotic stress, and mediate diverse cellular pathways in response to these signals. They are also known to interact with multiple effectors, affecting cellular and biochemical systems that regulate actin dynamics, reactive oxygen species production, proteolysis, and gene expression. RAC/ROPs are, thus, ideally suited as integrators for multiple signals and as coordinators of diverse cellular pathways to control growth, differentiation, development and defense responses. Recent findings that suggest how RAC/ROP signaling activity is regulated and how functional specificity can be achieved are discussed here. 相似文献