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Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitogen-activated protein (MAP) kinases are regarded as switch kinases in the phosphorylation cascade initiated by various agonists. We have investigated whether endothelins (ET), which are constrictor and mitogenic isopeptides, can increase MAP kinase activity in rat mesangial cells, using bovine myelin basic protein (MBP) as a substrate for an in vitro kinase assay. Treatment of quiescent mesangial cells with ET-1 rapidly stimulated a kinase activity which phosphorylated exogenous MBP. This stimulation was dose-dependent, with threshold responses at 1 nM-ET-1. Epidermal growth factor and thrombin also activated this kinase in mesangial cells. We also examined the ET signal transduction pathways leading to activation of MBP kinase. Pertussis toxin had no effect on ET-stimulated MBP kinase activity. Stimulation of protein kinase C by phorbol ester increased MBP kinase activity, and down-regulation of PKC partially inhibited ET-stimulated MBP kinase as well as phorbol ester-stimulated MBP kinase activity. Interestingly, genestein, an inhibitor of protein tyrosine kinases, partially inhibited MBP kinase stimulated by ET but not by phorbol esters. These results suggest that ET stimulates MBP kinase activity in rat mesangial cells via at least two pathways: one which is protein kinase C-dependent and a second one that involves a protein tyrosine kinase. Finally, by raising rabbit antibodies against the two forms of MAP kinase, p44mapk and p42mapk, we demonstrated that both isoforms are expressed in mesangial cells. Antibody alpha 1 Cp42 specifically immunoprecipitated p42mapk and allowed us to demonstrate that ET stimulates MBP kinase activity in the p42mapk immunocomplex. In conclusion, we have provided evidence that, in rat mesangial cells, MAP kinases are rapidly activated by ET-1, a regulatory process that involves at least protein kinase C activation and also a contribution of a tyrosine kinase not yet characterized.
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PMID:Endothelin rapidly stimulates mitogen-activated protein kinase activity in rat mesangial cells. 128 Jan 3

Incubation of Swiss 3T3 or L929 cells with tumor necrosis factor (TNF) leads to the rapid stimulation of several cytosolic Ser/Thr kinases active toward myelin basic protein, the S6 peptide (RRLSSLR), the G peptide (SPQPSRRGSESSEE), and Kemptide (LRRASLG). This confirms the hypothesis that kinases other than protein kinases A and C may be involved in the TNF signal transduction. Chromatography on Mono Q resolved multiple kinase peaks with each substrate tested and moreover revealed a TNF-mediated casein kinase-2 activation in both cell lines, measurable with the specific RRREEESEEE peptide or with the G peptide. The TNF-stimulated myelin basic protein kinases-1 and -2 were identified as extracellular signal-regulated kinases-2 and -1, respectively, based on their elution pattern on Mono Q chromatography, their inactivation by protein phosphatase action, their reaction with phosphothreonine and phosphotyrosine antibodies, and by their migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as 42- and 44-kDa proteins recognized by anti-extracellular signal-regulated kinase antibodies.
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PMID:Tumor necrosis factor stimulates multiple serine/threonine protein kinases in Swiss 3T3 and L929 cells. Implication of casein kinase-2 and extracellular signal-regulated kinases in the tumor necrosis factor signal transduction pathway. 128 78

Endothelins (ETs) are potent regulatory peptides that cause numerous phenotypic changes in glomerular mesangial cells including differential regulation of gene expression and mitogenesis. Although the second messengers produced by activated ET receptors are well characterized, little is known about pathways of nuclear signaling. In this report, we evaluate the role of a well-characterized effector linked to ET receptor activation, protein kinase C, in the stimulation of mitogen-activated protein kinase (p42-44mapk) and the induction of protooncogene c-fos. Stimulation of protein kinase C by phorbol ester was sufficient to increase p42-44mapk activity and induce c-fos. When ET-1 was added to mesangial cells depleted of protein kinase C, the increase in p42-44mapk was attenuated and the induction of c-fos was abolished. Taken together with previous data, these experiments suggest that protein kinase C, p42-44mapk, and c-fos constitute a pathway by which ET-1 regulates expression of mesangial cell genes. These effectors might have relevance to the role of ET-1 in cell growth and vascular remodeling.
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PMID:Protein kinase C regulates activation of mitogen-activated protein kinase and induction of proto-oncogene c-fos by endothelin-1. 128 79

To investigate the function of the RB protein, we have studied cellular RB binding proteins and protein kinases responsible for phosphorylation of the RB protein. (1) We purified a cellular RB-associated protein p56 which competes with SV40 large T antigen for binding to the RB protein. (2) In another experiment, we screened expression libraries of U937 monocytic leukemia cell line by West-Western method and obtained two cDNA clones that encode RB binding proteins. (3) The RB protein was found to be phosphorylated by cdk2 and MAP kinase in vitro. Most of the sites phosphorylated in vitro are the same as those phosphorylated in vivo and the time course of activation of cdk2 in the cell cycle were similar to that of phosphorylation of the RB protein.
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PMID:Phosphorylation of the anti-oncogene products and control of the cell cycle. 130 98

When PC12D cells, a subline of PC12 cells, were cultured with nerve growth factor (NGF), outgrowth of neurites was promoted even when RNA synthesis was blocked. This property of PC12D cells may enable us to resolve the mechanism of the outgrowth of neurites that is induced in a transcription-independent manner. The outgrowth of neurites from PC12D cells was also stimulated in response to fibroblast growth factor (FGF) and was slightly stimulated in response to epidermal growth factor (EGF). The brief exposure of intact PC12D cells not only to NGF but also to FGF or to EGF stimulated a protein kinase activity in extracts of such cells that catalyzed phosphorylation of microtubule-associated protein 1 (MAP-1) and MAP-2 in vitro. Similar dose-response relationships for the effects of NGF and of FGF on the activation of the kinase and on the outgrowth of neurites were observed. The effects of combinations of NGF and GFG or EGF were not additive in terms of either the outgrowth of neurites or the increase in the kinase activity. Treatment of cells with phorbol 12-myristate 13-acetate (PMA) also stimulated the kinase activity that phosphorylated MAPs in vitro. However, the level of the enzymatic activity that resulted from the combined treatment of cells with PMA and NGF was additive, as is the case with dibutyryl cyclic AMP and NGF. These findings suggest that NGF, FGF, and EGF may stimulate the activity of the same MAP kinase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of microtubule-associated protein kinase in PC12D cells in response to both fibroblast growth factor and epidermal growth factor and concomitant stimulation of the outgrowth of neurites. 131 Jul 25

T cell signaling via the CD4 surface antigen is mediated by the associated tyrosyl protein kinase p56lck. The 42-kilodalton mitogen-activated protein (MAP) kinase (p42mapk) was tyrosyl-phosphorylated and activated after treatment of the murine T lymphoma cell line 171CD4+, which expresses CD4, with antibody to CD3. Treatment of the CD4-deficient cell line 171 with the same antibody did not result in phosphorylation or activation of p42mapk. Purified p56lck both tyrosyl-phosphorylated and stimulated the seryl-threonyl phosphotransferase activity of purified p44mpk, a MAP kinase isoform from sea star oocytes. A synthetic peptide modeled after the putative regulatory phosphorylation site in murine p42mapk (Tyr185) was phosphorylated by p56lck with a similar Vmax, but a fivefold lower Michaelis constant (Km) than a peptide containing the Tyr394 autophosphorylation site from p56lck. MAP kinases may participate in protein kinase cascades that link Src family protein-tyrosyl kinases to seryl-threonyl kinases such as those encoded by rsk and raf, which are putative substrates of MAP kinases.
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PMID:Tyrosyl phosphorylation and activation of MAP kinases by p56lck. 131 Nov 28

Treatment of PC12 cells with nerve growth factor (NGF) induces a rapid increase in tyrosine phosphorylation of multiple cellular proteins. Expression of a dominant inhibitory Ras mutant specifically blocked NGF- and TPA-induced tyrosine phosphorylation of two proteins of approximately 42 and 44 kd. Conversely, expression of an oncogenic variant of Ras induced tyrosine phosphorylation of the same 42 and 44 kd proteins. The 44 kd protein was immunoprecipitated with an antibody directed against extracellular signal-regulated kinase 1/mitogen-activated protein kinase (MAPK) and the 42 kd protein comigrated with a 42 kd MAPK, indicating that at least one and probably both Ras-regulated phosphoproteins are MAPKs. In addition, MAPK activation, as measured by in vitro phosphorylation of myelin basic protein, was also regulated by Ras. Ras was not required for NGF-induced activation of Trk or tyrosine phosphorylation of PLC-gamma 1. Thus, NGF-induced tyrosine phosphorylation occurs both prior to and following Ras action, and Ras plays a critical role in the NGF- and TPA-induced tyrosine phosphorylation of MAPKs.
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PMID:Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases. 131 92

MAP kinase is thought to play a pivotal role not only in the growth factor-stimulated signalling pathway but also in the M phase phosphorylation cascade downstream of MPF. MAP kinase is fully active only when both tyrosine and threonine/serine residues are phosphorylated. We have now identified and purified a Xenopus MAP kinase activator from mature oocytes that is able to induce activation and phosphorylation on tyrosine and threonine/serine residues of an inactive form of Xenopus MAP kinase. The Xenopus MAP kinase activator itself is a 45 kDa phosphoprotein and is inactivated by protein phosphatase 2A treatment in vitro. Microinjection of the purified activator into immature oocytes results in immediate activation of MAP kinase. Further experiments using microinjection as well as cell free extracts have shown that Xenopus MAP kinase activator is an intermediate between MPF and MAP kinase. Thus, MAP kinase activator plays a key role in the phosphorylation cascade.
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PMID:Xenopus MAP kinase activator: identification and function as a key intermediate in the phosphorylation cascade. 131 68

Up to 1 mol of phosphoryl groups was incorporated per mol of eukaryotic protein synthesis initiation factor (eIF) 4E following incubation of purified preparations of this factor with purified preparations of a protamine kinase from bovine kidney cytosol. By contrast, purified preparations of two forms of mitogen-activated protein kinase, casein kinase II and two forms of a distinct autophosphorylation-activated protein kinase exhibited little activity, if any, with eIF-4E. Together with previous observations, the results indicate that the protamine kinase could contribute to the insulin-stimulated phosphorylation of eIF-4E.
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PMID:Protamine kinase phosphorylates eukaryotic protein synthesis initiation factor 4E. 131 30

Mitogen-activated protein (MAP) kinases are activated in response to a variety of extracellular stimuli by phosphorylation on tyrosine and threonine residues. Xp42 is a Xenopus laevis MAP kinase that is activated during oocyte maturation. Modified forms of Xp42 that lacked enzymatic activity or either of the phosphorylation sites were expressed in Xenopus oocytes. When meiotic maturation was induced with progesterone, each mutant Xp42 was phosphorylated, indicating that at least one kinase was activated that can phosphorylate Xp42 on tyrosine and threonine. Phosphorylation of one residue is not strictly dependent on phosphorylation of the other.
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PMID:Requirements for phosphorylation of MAP kinase during meiosis in Xenopus oocytes. 131 86


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