Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the purification to near homogeneity of a 45-kDa phorbol ester-stimulated protein kinase that phosphorylates and activates the Erk-1 gene product. This kinase, which we provisionally denote MEK for MAPK/Erk kinase, phosphorylated kinase-inactive Erk-1 protein primarily on a tyrosine residue and, to a lesser extent, on a threonine. We extend our previous results and show that two forms of purified MEK activated the myelin basic protein kinase encoded by Erk-1. MEK was inactivated by the serine/threonine phosphatase 2A but not by the protein-tyrosine phosphatase 1B. Sequence analysis of peptides generated by trypsin digestion of MEK revealed similarity to the proteins encoded by the Schizosaccharomyces pombe byr1 and Saccharomyces cerevisiae STE7 genes. These data are discussed with regard to a possible signal transduction mechanism.
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PMID:Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product. 138 7

Essential to signal transduction are mechanisms of "cross-talk" to coordinate different pathways. This study shows that stimulation of serine/threonine protein kinases activates protein-tyrosine phosphatase (PTPase; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48). More than 95% of intracellular PTPase was in the particulate fraction of various cell lines and was extracted with detergent as a 150-kDa complex that contained a 55-kDa catalytic subunit. The complex was activated by protease digestion, which changed its substrate specificity coincident with reduction in size. The complex was dissociated by treatment of the membrane fraction with 3 M LiBr. Treatment of intact cells with isoproterenol, forskolin, or cAMP analogues to stimulate cAMP-dependent protein kinase (PKA) or with phorbol ester or dioctanoylglycerol to stimulate Ca2+/phospholipid-dependent protein kinase (PKC) produced activation of membrane PTPase complex without a change in its size. Inhibition of protein-serine/threonine phosphatases with okadaic acid or fluoride also resulted in activation of the membrane PTPase. These results support a model for regulation of PTPase by phosphorylation and dephosphorylation of serine/threonine residues in a regulatory component complexed with the 55-kDa PTPase catalytic subunit. This mechanism may be important in regulating sensitivity to extracellular signals transduced via tyrosine phosphorylation and in the synchronization of events during the cell cycle.
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PMID:Activation of membrane protein-tyrosine phosphatase involving cAMP- and Ca2+/phospholipid-dependent protein kinases. 165 Apr 78

The onset of M phase requires the activation of the pp34 protein kinase in all eukaryotes thus far examined. In Schizosaccharomyces pombe, pp34 is phosphorylated on Tyr15, and dephosphorylation of this residue regulates the initiation of mitosis. In this study, it is shown that dephosphorylation of Tyr15 triggered activation of the pp34-cyclin complex from fission yeast, that a human protein-tyrosine phosphatase can catalyze this event both in vitro and in vivo, and that activation of fission yeast pp34 does not require threonine dephosphorylation. The complementary DNA that encoded the tyrosine phosphatase replaced the mitotic activator p80cdc25, closely associating the cdc25(+)-activating pathway with tyrosine dephosphorylation of pp34.
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PMID:Complementation of the mitotic activator, p80cdc25, by a human protein-tyrosine phosphatase. 170 21

A protein-tyrosine phosphatase LC-PTP is preferentially expressed in hematopoietic cells and is an early response gene in lymphokine stimulated cells. Here, we found the LC-PTP mRNA induction by IL-2 was markedly inhibited by several tyrosine kinase inhibitors. The induction required both the acidic and serine-rich regions of the IL-2 receptor beta chain (IL-2R beta) in mouse IL-3-dependent pro-B BAF-B03 transfectants. This is strikingly different from the induction of c-myc gene expression, which requires the serine-rich region alone. In addition, overexpression of activated-Lck or -Raf kinases resulted in augmented LC-PTP mRNA expression in myeloid cell line 32D transfectants. Considering the previous findings that the acidic region of the IL-2R beta is responsible for association with Lck and activation of Raf kinase, IL-2-induced expression of LC-PTP mRNA may be primarily transduced through a Lck-Raf mediated signaling pathway.
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PMID:IL-2-induced gene expression of protein-tyrosine phosphatase LC-PTP requires acidic and serine-rich regions within IL-2 receptor beta chain. 755 30

Protein-tyrosine phosphorylation has long been regarded as an exclusively eukaryotic phenomenon. Although some non-eukaryotes, mainly viruses, possess genes encoding protein-tyrosine kinases or protein-tyrosine phosphatases, these were probably appropriated from the eukaryotic hosts that constitute the sites of action of these enzymes. Herein we identify a gene, iphP, from the chromosome of the cyanobacterium Nostoc commune UTEX 584 that contains the His-Cys-Xaa-Ala-Gly-Xaa-Xaa-Arg sequence characteristic of known protein-tyrosine phosphatases. The expressed gene product, IphP, displayed protein-tyrosine phosphatase activity toward phosphotyrosine residues on reduced, carboxyamidomethylated, and maleylated lysozyme with optimum activity at pH 5.0. In addition, IphP dephosphorylated the phosphoseryl groups on casein that had been phosphorylated by the cAMP-dependent protein kinase. Cell lysates of N. commune probed with antibodies to phosphotyrosine indicated the presence of a tyrosine-phosphorylated protein of M(r) approximately 85 kDa. This tyrosine-phosphorylated protein was detected in cells grown in the presence of combined nitrogen but not in nitrogen-deficient media that induces the formation of differentiated N2-fixing cells (heterocysts). Together, these data suggest a role for protein-tyrosine phosphorylation in regulating cellular functions in this cyanobacterium. IphP is the first protein-tyrosine phosphatase to be discovered that is encoded by the chromosomal DNA of any prokaryote. Given the free-living nature of N. commune and the phylogenetic antiquity of the cyanobacteria, these findings suggest for the first time the existence of a protein-tyrosine phosphatase of genuine, unambiguous prokaryotic ancestry, thus raising fundamental questions as to the origin and role of tyrosine phosphorylation.
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PMID:A protein-tyrosine/serine phosphatase encoded by the genome of the cyanobacterium Nostoc commune UTEX 584. 768 25

The transforming protein of simian sarcoma virus is homologous to the platelet-derived growth factor (PDGF) B-chain. Fibroblasts transformed with simian sarcoma virus constitutively produce a growth factor that stimulates the endogenous tyrosine kinase of PDGF receptors in an autocrine manner. Autophosphorylation of PDGF receptors upon ligand stimulation provides binding sites for Src homology 2 domains of intracellular signaling molecules, which thereby become activated. We have characterized the PDGF receptor-mediated signal transduction in NIH 3T3 cells transformed with a PDGF B-chain cDNA (Sis 3T3 cells) in the absence and presence of suramin, a polyanionic compound that quenches PDGF-induced mitogenicity and reverts the transformed phenotype of the Sis 3T3 cells. Our data show that in the presence of suramin the general level of tyrosine phosphorylation was decreased. Nevertheless, autophosphorylated receptors complexed with substrates persisted in the cells. Suramin had no effect on activation of phosphatidylinositol 3'-kinase or on tyrosine phosphorylation of phospholipase C-gamma and GTPase-activating protein of Ras. On the other hand, kinase activation of Src and Raf-1, phosphorylation of protein-tyrosine phosphatase 1D/Syp and Shc, and complex formation with Grb2 were greatly diminished by suramin. A possible explanation for our findings is that different PDGF receptor-coupled signaling pathways are active in different structural or functional compartments in the cell. Those pathways that are not affected by suramin might elicit distinct cellular responses, which are not sufficient for growth and transformation.
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PMID:Compartmentalization of autocrine signal transduction pathways in Sis-transformed NIH 3T3 cells. 773 Mar 19

Phosphorylation of proteins catalysed by protein kinases is associated with central functions in growth and proliferation of the eukaryotic cell, and kinases are particularly important in the signal transduction pathways. Enterobacterial protein kinases are structurally and functionally different from eukaryotic protein kinases, and no prokaryotic kinase has so far been described implicating a direct role for this activity in virulence. Virulent Yersinia possess a common virulence plasmid that encodes a number of secreted proteins (Yops), of which YopH has protein-tyrosine phosphatase activity with a key function in the block of phagocytosis by the pathogen. Here we report that the virulence plasmid of Yersinia pseudotuberculosis encodes a secreted protein kinase (YpkA) with extensive homology to eukaryotic Ser/Thr protein kinases. Specific mutants of ypkA resulted in avirulent strains. Thus, YpkA is, to our knowledge, the first reported prokaryotic secreted protein kinase involved in pathogenicity, presumably by interfering with the signal transduction pathways of the target cell.
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PMID:A secreted protein kinase of Yersinia pseudotuberculosis is an indispensable virulence determinant. 844 68

Previously we found that rat mesangial cells express 3CH134/CL100 protein-tyrosine phosphatase (PTPase) in response to reactive oxygen intermediates (ROIs), and we now extend these studies to glomerulonephritis (GN), where ROI have been demonstrated to play a role. The rat homologue of 3CH134/CL100 was cloned from a rat macrophage cDNA library. The rat 3CH134/CL100 mRNA was strongly induced in the lung, liver, and heart the first day after birth, suggesting that hyperoxic adaption might be involved in the induction of the PTPase mRNA. In anti-glomerular basement membrane (GBM) antibody (Ab) GN in rats, the 3CH134/CL100 PTPase mRNA was expressed in glomeruli as early as 30 minutes after anti-GBM Ab injection. The 3CH134/CL100 mRNA expression was modulated by the ROI scavenger dimethylthiourea (DMTU), indicating that its induction was ROI related. In contrast to the glomerular lesion, PTPase mRNA expression was not induced in experimental tubulointerstitial nephritis. In situ hybridization suggested that mesangial and some infiltrating cells were the major glomerular cell sources of the PTPase mRNA. These results indicate that rat CCH134/CL100 PTPase is actively induced in glomeruli as part of an acute immune injury at least in part related to oxidative stress. PTPase induction in GN and potentially other forms of inflammation may play an important regulatory role in protein kinase signaling pathways.
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PMID:Oxidative stress-inducible protein tyrosine phosphatase in glomerulonephritis. 858 53

A membrane-associated form of Raf-1 in v-Ras transformed NIH 3T3 cells can be inactivated by protein phosphatases regulated by GTP. Herein, a distinct protein-tyrosine phosphatase (PTPase) in membrane preparations from v-Ras transformed NIH 3T3 cells was found to be activated by guanyl-5'-yl imidodiphosphate (GMPPNP) and was identified as an effector for pertussis toxin (PTx)-sensitive G-protein alpha subunits. PTPase activation was blocked by prior treatment of cells with PTx. PTPase activation by GTP, but not GMPPNP, was transient. A GMPPNP-stimulated PTPase (PTPase-G) co-purified with Galphai/o subunits during Superose 6 and Mono Q chromatography. PTPase-G activity in Superose 6 fractions from GDP-treated membranes was reconstituted by activated Galphai/o, but not G beta gamma, subunits. PTPase-G may contribute to GMPPNP-stimulated inactivation of Raf-1 in v-Ras cell membranes because Raf-1 inactivation was PTx-sensitive and PTPase-G inactivated exogenous Raf-1.
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PMID:Inactivation of raf-1 by a protein-tyrosine phosphatase stimulated by GTP and reconstituted by Galphai/o subunits. 862 10

Rapid tyrosine phosphorylation of key cellular proteins is a crucial event in signal transduction. The regulatory role of protein-tyrosine phosphatases (PTPs) in this process was explored by studying the effects of a powerful PTP inhibitor, pervanadate, on the activation of the mitogen-activated protein (MAP) kinase cascade. Treatment of HeLa cells with pervanadate resulted in a marked inhibition of PTP activity, accompanied by a drastic increase in tyrosine phosphorylation of cellular proteins. The increased tyrosine phosphorylation coincided with the activation of the MAP kinase cascade as indicated by enzymatic activity assays of MEK (MAP kinase/ERK-kinase) and MAP kinase and gel mobility shift analyses of Raf-1 and MAP kinase. The activation was sustained but reversible. Upon removal of pervanadate, both tyrosine phosphorylation and MAP kinase activation declined to basal levels. Therefore, inhibition of PTP activity is sufficient per se to initiate a complete MAP kinase activation program.
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PMID:Activation of mitogen-activated protein (MAP) kinase pathway by pervanadate, a potent inhibitor of tyrosine phosphatases. 870 41


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