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:3.4.11.18 (MAP)
7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In animals, MAP kinase plays a key role in growth factor-stimulated signalling and in mitosis. The isolation of a Medicago sativa cDNA clone MsK7 which shows 52% identity to animal MAP kinases is reported. The deduced protein sequence shows all the important structural features of MAP kinases and also contains the highly conserved Thr-183 and Tyr-185 residues. Northern analysis of synchronized alfalfa cells showed that the MsK7 kinase gene is expressed at low levels in G1 phase but at higher levels in S and G2 phases of the cell cycle. In the plant, only stems and roots were found to contain MAP kinase MsK7 mRNA. Southern and PCR analyses indicated that alfalfa contains at least four highly related MAP kinase genes.
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PMID:The plant homologue of MAP kinase is expressed in a cell cycle-dependent and organ-specific manner. 822 Apr 66

Ag-induced cross-linking of IgE bound to its high affinity receptor (Fc epsilon RI) at the surface of basophils or mast cells triggers a number of biochemical events culminating in the release of several inflammatory mediators. In rat basophilic leukemia (RBL-2H3) cells expressing the G protein-coupled m1 muscarinic receptor, Ag/IgE-induced cross-linking of Fc epsilon RI, calcium ionophore A23187, and carbachol through M1 receptors stimulated tyrosine phosphorylation of several proteins, including two of 42 and 44 kDa. Proteins of identical molecular masses were recognized by anti-MAP-kinase antibodies, and these immunoreactive proteins exhibited in part a slightly increased molecular mass on SDS polyacrylamide gels after incubation of cells with secretory stimuli. All stimuli led to the activation of MAP kinase, which co-purified on Mono Q chromatography with 42- and 44-kDa proteins, which were tyrosine phosphorylated in response to secretory stimuli and reacted with anti-(MAP kinase) antibodies. Finally, 42- and 44-kDa proteins immunoprecipitated by anti-MAP-kinase antibodies and anti-phosphotyrosine antibodies were recognized by anti-phosphotyrosine and anti-MAP-kinase antibodies, respectively. Primarily threonine and tyrosine residues were found to be phosphorylated in 42- and 44-kDa proteins immunoprecipitated from [32P]phosphate-labeled cells that had been treated with secretory stimuli. The dose dependence of secretagogue-induced MAP kinase activation correlated with that of increases in serotonin release from activated cells, and the maximum of MAP kinase activation coincided with the maximum rate of secretion. Down-regulation or inhibition of protein kinase C as well as incubation of cells with the tyrosine kinase inhibitor genistein markedly inhibited MAP kinase activation in parallel with serotonin release. Taken together, these findings demonstrate that 42- and 44-kDa MAP kinases are activated in response to secretory stimuli and provide some evidence for a functional link between MAP kinase activation and signaling events leading to mediator release in RBL cells.
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PMID:Stimulation of mitogen-activated protein kinase activity by different secretory stimuli in rat basophilic leukemia cells. 825 95

We previously reported two cDNAs for MAP kinases (cATMPK1 and cATMPK2) from a dicot plant, Arabidopsis thaliana. We describe here the cloning and characterization of five additional cDNAs encoding novel MAP kinases in Arabidopsis, cATMPK3, cATMPK4, cATMPK5, cATMPK6, and cATMPK7. The amino acid residues corresponding to the sites of phosphorylation (Thr-Glu-Tyr) that are involved in the activation of animal MAP kinases are conserved in all the seven putative ATMPK proteins. Genes for MAP kinases in Arabidopsis constitute a family that contains more than seven members. Sequence analysis suggests that there are at least three subfamilies in the family of Arabidopsis genes for MAP kinases.
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PMID:ATMPKs: a gene family of plant MAP kinases in Arabidopsis thaliana. 828 7

MEK1 is a dual specificity kinase that phosphorylates and activates the Erk/MAP kinases Erk-1 and Erk-2 by phosphorylating them on threonine and tyrosine. We report the cloning of a second MEK-like complementary DNA, Mek2, which predicts a protein of a molecular weight of 44,500. The MEK2 protein bears substantial sequence homology to MEK1, except at its amino terminus, and at a proline-rich region insert between the conserved kinase subdomains 9 and 10. MEK1 and MEK2 are shown to be encoded by different genes and are located on murine chromosomes 9 and 10, respectively. Northern analysis indicates that Mek2 is expressed at low levels in adult mouse brain and heart tissue, and at higher levels in other tissues examined. Low expression levels of Mek2 in brain tissue are in contrast to the high levels of Mek1 expressed in brain. Mek2 is expressed at high levels in neonatal brain, however. Recombinant MEK2 produced in bacteria phosphorylates a kinase-inactive Erk-1 on tyrosine and threonine, whereas a kinase-inactive mutant MEK2 does not. These findings suggest that MEK2 is a member of a multigene family.
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PMID:MEK2 is a kinase related to MEK1 and is differentially expressed in murine tissues. 829 98

Production of reactive oxygen metabolites by the NADPH oxidase is an essential mechanism underlying the microbicidal role of phagocytes. Receptor-mediated activation of the oxidase was originally thought to be mediated by calcium and/or by protein kinase C (PKC). However, recent evidence suggests that additional signalling pathways exist. In this article the possible role of tyrosine phosphorylation is discussed. In addition, results obtained using an in vitro kinase renaturation assay are described. The latter assay revealed the existence of at least four serine/threonine kinases that are activated in cells stimulated with chemoattractants. One of these, of molecular weight 41,000 was identified as a member of the ERK or MAP-kinase family. The existence of multiple, possibly redundant or synergistic signaling pathways is considered.
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PMID:Involvement of multiple kinases in neutrophil activation. 831 67

Mitogen-activated protein kinases (MAP kinases) or meiosis-activated myelin basic protein kinase (p44mpk) are known to be activated by a mechanism involving dual phosphorylation at both tyrosine and serine/threonine in response to many extracellular stimuli. There has been considerable speculation as to whether MAP kinases are autophosphorylated and activated by an upstream protein kinase (MAP kinase kinase) or an activator of autophosphorylation or both. Here we report that the ets-related proteins elk-1 and delta elk-1 to be potential physiological substrates and activators of MAP kinases. Our results demonstrate for the first time that MAP kinase activators can also be non-kinase proteins that enhance the autophosphorylation and activation of MAP kinase. These findings could establish a general mechanism wherein specific MAP kinase activator protein(s) may function by interacting with MAP kinases ensuring a conformational change and stimulating their autophosphorylation and activation property. Our results also suggest that the amino-terminal truncated elk-1 proteins are better activators of MAP kinase than full length proteins indicating the presence of a potential negative regulatory region which may control the kinase activator function of elk-1 proteins. Our results suggest differential regulation of elk-1 and delta elk-1 proteins in fibroblasts stimulated by epidermal growth factor implicating a key role for these proteins in the signal transduction pathway. These results establish the presence of an alternative pathway for activation of MAP kinases. Thus we propose that elk-1 proteins may represent key intermediates which would transmit signals arriving at the surface of the cell from activated receptors to downstream MAP kinases in the cytoplasm to reach the transcriptional factors in the nucleus.
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PMID:Elk-1 proteins are phosphoproteins and activators of mitogen-activated protein kinase. 833 45

MAP kinases p42mapk and p44mapk participate in a protein kinase cascade(s) important for signaling in many cell types and contexts. Both MAP kinases are activated in vitro by MAP kinase kinase, a protein-tyrosine and threonine kinase. A MAP kinase kinase cDNA was isolated from a rat kidney library by using peptide sequence data we obtained from MAP kinase kinase isolated from rabbit skeletal muscle. The deduced sequence, containing 393 amino acids (predicted mass, 43.5 kDa), is most similar to byr1 (Bypass of ras1), a yeast protein kinase functioning in the mating pathway induced by pheromones in Schizosaccharomyces pombe. An unusually large insert is present in MAP kinase kinase between domains IX and X and may contribute to protein-protein interactions with MAP kinase. Major (2.7 kilobases) and minor (1.7 kilobases) transcripts are widely expressed in rat tissues and appear to be derived from a single gene.
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PMID:Molecular structure of a protein-tyrosine/threonine kinase activating p42 mitogen-activated protein (MAP) kinase: MAP kinase kinase. 838 Apr 94

The induction of T-cell growth by the T-cell antigen receptor (TcR) is dependent on a co-ordinated process of phosphorylation and dephosphorylation of intracellular proteins. An intermediary in this signalling pathway is the serine kinase, p42 mitogen-activated protein kinase (p42MAPK), also known as microtubule-associated protein-2 kinase (MAP-2K). MAP-kinase is activated upon the acquisition of tyrosine as well as threonine phosphate groups and removal of either by specific tyrosine or serine/threonine phosphatases abrogates kinase activity. Okadaic acid (OA), a tumour promoter and potent inhibitor of type 1 and 2A serine/threonine protein phosphatases (PP1 and PP2A), induced MAP-kinase activity in Jurkat T cells in a dose-dependent fashion with optimal effect at 1 microM. Compared to rapid activation (peak < 10 min) of MAP-kinase by another tumour promoter, the phorbol ester, PMA, the effect of OA was delayed (> 30 min) and more sustained. In spite of activating a growth-promoting kinase, OA differed from PMA by its lack of mitogenic activity and failure to induce CD25 [interleukin-2R alpha (IL-2R alpha)] expression in normal human T cells. This implies that PP1 and PP2A also act downstream of MAP-kinase to facilitate later cell cycle events. PMA induced a 42,000 MW tyrosine phosphoprotein which co-electrophoresed and co-chromatographed with ERK-2, a p42 MAP-kinase. Although OA induced an identical Mono-Q peak, there was less avid tyrosine phosphorylation of p42. OA also differed from PMA to the extent by which it induced mobility shift of the tyrosine protein kinase, p56lck, which has been implicated in p42MAPK activation in T cells. Taken together, these results indicate that OA and PMA exert both overlapping as well as divergent effects on lymphocyte growth pathways.
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PMID:Contrasting effects of two tumour promoters, phorbol myristate acetate and okadaic acid, on T-cell responses and activation of p42 MAP-kinase/ERK-2. 838 30

Mitogen-activated protein kinases (p42mapk and p44mapk) are serine/threonine kinases that are activated rapidly in cells stimulated with various extracellular signals. This activation is mediated via MAP kinase kinase (p45mapkk), a dual specificity kinase which phosphorylates two key regulatory threonine and tyrosine residues of MAP kinases. We reported previously that the persistent phase of MAP kinase activation is essential for mitogenically stimulated cells to pass the "restriction point" of the cell cycle. Here, using specific polyclonal antibodies and transfection of epitope-tagged recombinant MAP kinases we demonstrate that these signaling protein kinases undergo distinct spatio-temporal localization in growth factor-stimulated cells. In G0-arrested hamster fibroblasts the activator p45mapkk and MAP kinases (p42mapk, p44mapk) are mainly cytoplasmic. Subsequent to mitogenic stimulation by serum or alpha-thrombin both MAP kinase isoforms translocate into the nucleus. This translocation is rapid (seen in 15 min), persistent (at least during the entire G1 period up to 6 h), reversible (by removal of the mitogenic stimulus) and apparently 'coupled' to the mitogenic potential; it does not occur in response to nonmitogenic agents such as alpha-thrombin-receptor synthetic peptides and phorbol esters that fail to activate MAP kinases persistently. When p42mapk and p44mapk are expressed stably at high levels, they are found in the nucleus of resting cells; this nuclear localization is also apparent with kinase-deficient mutants (p44mapk T192A or Y194F). In marked contrast the p45mapkk activator remains cytoplasmic even during prolonged growth factor stimulation and even after high expression levels achieved by transfection. We propose that the rapid and persistent nuclear transfer of p42mapk and p44mapk during the entire G0-G1 period is crucial for the function of these kinases in mediating the growth response.
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PMID:Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase (p45mapkk) in fibroblasts. 839 45

The mitogen-activated protein kinases (MAP kinases) p42mapk and p44mapk are serine/threonine kinases rapidly activated in cells stimulated with various extracellular signals by dual phosphorylation of tyrosine and threonine residues. They are thought to play a pivotal role in integrating and transmitting transmembrane signals required for growth and differentiation. Here we demonstrate that activation of these ubiquitously expressed MAP kinases is essential for growth. To specifically suppress MAP kinase activation in fibroblasts, we transiently expressed either the entire p44mapk antisense RNA or p44mapk kinase-deficient mutants (T192A or Y194F). As expected, and through independent mechanisms, both approaches strongly inhibited MAP kinase activation. The antisense reduced the expression of endogenous p42mapk and p44mapk by 90%, whereas overexpression of the T192A mutant inhibited growth factor activation of both endogenous MAP kinases by up to 70%. As a consequence, we found that the antisense as well as the T192A mutant of p44mapk inhibited growth factor-stimulated gene transcription (collagenase promoter assay with chloramphenicol acetyltransferase reporter) and cell growth. These effects were proportional to the extent of MAP kinase inhibition and reversed by coexpression of the wild-type p44mapk. Therefore we conclude that growth factor activation of p42mapk and p44mapk is an absolute requirement for triggering the proliferative response.
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PMID:Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation. 839 1


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