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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)

Mitogen-activated protein kinase cascades are conserved in fungal, plant, and metazoan species. We expressed murine MAP kinase kinase kinase (MEKK) in the yeast Saccharomyces cerevisiae to determine whether this kinase functions as a general or specific activator of genetically and physiologically distinct MAP-kinase-dependent signaling pathways and to investigate how MEKK is regulated. Expression of MEKK failed to correct the mating deficiency of a ste11 delta mutant that lacks an MEKK homolog required for mating. MEKK expression also failed to induce expression of a reporter gene controlled by the HOG1 gene product (Hog1p), a yeast MAP kinase homolog involved in response to osmotic stress. Expression of MEKK did correct the cell lysis defect of a bck1 delta mutant that lacks an MEKK homolog required for cell-wall assembly. MEKK required the downstream MAP kinase homolog in the BCK1-dependent pathway, demonstrating that it functionally replaces the BCK1 gene product (Bck1p) rather than bypassing the pathway. MEKK therefore selectively activates one of three distinct MAP-kinase-dependent pathways. Possible explanations for this selectivity are discussed. Expression of the MEKK catalytic domain, but not the full-length molecule, corrected the cell-lysis defect of a pkc1 delta mutant that lacks a protein kinase C homolog that functions upstream of Bck1p. MEKK therefore functions downstream of the PKC1 gene product (Pkc1p). The N-terminal noncatalytic domain of MEKK, which contains several consensus protein kinase C phosphorylation sites, may, therefore, function as a negative regulatory domain. Protein kinase C phosphorylation may provide one mechanism for activating MEKK.
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PMID:Mammalian mitogen-activated protein kinase kinase kinase (MEKK) can function in a yeast mitogen-activated protein kinase pathway downstream of protein kinase C. 819 59

Mitogen-activated protein kinases (MAP kinases) are active only when phosphorylated. Here we examine whether the activation of Xenopus p42 MAP kinase might involve changes in its association with other proteins as well as changes in its phosphorylation state. We find that when p42 MAP kinase is phosphorylated and active, it is monomeric, and that when p42 MAP kinase is nonphosphorylated and inactive, about half of it is monomeric and half is a component of a 110-kDa complex. We identify Rsk, an 82-kDa protein kinase that can be phosphorylated and partially activated by p42 MAP kinase, as being specifically associated with inactive p42 MAP kinase. It is possible that the complex of inactive p42 MAP kinase and inactive Rsk acts as a single signal reception particle and that the activation of the two kinases may be better described as a fork in a bifurcating signal transduction pathway than as successive levels in a kinase cascade.
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PMID:Evidence that inactive p42 mitogen-activated protein kinase and inactive Rsk exist as a heterodimer in vivo. 820 12

Vasoactive intestinal peptide (VIP), a neuropeptide coupled with adenylate cyclase, was found to induce neurite extension of PC12h cells. Neurites appeared within 1 h after addition of VIP and extended for at least 24 h. The half-maximal concentration for the effect of VIP was 50 nM. In addition to the morphological change, VIP induced expression of VGF protein, a neuron-specific protein associated with neuronal differentiation. Western blotting with anti-phosphotyrosine antibody showed that VIP stimulated tyrosine phosphorylation of two proteins of 42 and 44 kDa, which may be two isoforms of MAP kinase, erk1 and erk2. Activation of MAP kinases was confirmed by ion-exchange chromatography on a Mono Q column, from which VIP-induced kinase activity was co-eluted with MAP kinase-immunoreactivity. Tyrosine-phosphorylation of MAP kinases was also stimulated by forskolin or dibutyryl cAMP, indicating that activation of MAP kinases by VIP might be mediated by cAMP. These results suggest that VIP-induced differentiation of PC12 cells is associated with cAMP-dependent activation of MAP kinases.
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PMID:Vasoactive intestinal peptide induces differentiation and MAP kinase activation in PC12h cells. 820 80

We have isolated and sequenced a MAP (mitogen-activated protein) kinase-type cDNA from a tobacco (Nicotiana tabacum L.) cell suspension cDNA library by screening with a PCR fragment amplified from the same library with oligonucleotide primers corresponding to two sequences conserved in yeast and animal MAP kinases. The tobacco sequence, ntf3, shows 45-54% identity to various members of the MAP kinase family at the protein level. Northern experiments showed that ntf3 is expressed in all tobacco tissues tested, including pollen isolated at different developmental stages. Southern analysis indicated that, as in other organisms, there is a family of MAP kinase genes in tobacco. In complementary tests, ntf3 could not substitute the yeast MAP kinase genes fus3 and kss1.
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PMID:Isolation and characterization of a tobacco cDNA clone encoding a putative MAP kinase. 821 89

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

Mitogenic stimulation of cells induces rapid and transient activation of MAP kinases. Here we report that a growth factor-inducible gene, 3CH134, encodes a dual specificity phosphatase that dephosphorylates and inactivates p42MAPK both in vitro and in vivo. In vitro, 3CH134 protein dephosphorylates both T183 and Y185 in p42MAPK. In serum-stimulated normal fibroblasts, the kinetics of inactivation of p42MAPK coincides with the appearance of newly synthesized 3CH134 protein, and the protein synthesis inhibitor cycloheximide leads to persistent activation of MAP kinase. Expression of 3CH134 in COS cells leads to selective dephosphorylation of p42MAPK from the spectrum of phosphotyrosyl proteins. 3CH134 blocks phosphorylation and activation of p42MAPK mediated by serum, oncogenic Ras, or activated Raf, whereas the catalytically inactive mutant of the phosphatase, Cys-258-->Ser, augments MAP kinase phosphorylation under similar conditions. The mutant 3CH134 protein also forms a physical complex with the phosphorylated form of p42MAPK. These findings suggest that 3CH134 is a physiological MAP kinase phosphatase; we propose the name MKP-1 for this phosphatase.
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PMID:MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. 822 88

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

Skeletal muscle is a major target of insulin action. The possible role of MAP kinase activation in insulin receptor signaling in muscle was examined. After a 48-hr fast, rats were injected intravenously with insulin or saline, muscles were excised after 3-20 min, homogenized, and MAP kinases were partially purified by ammonium sulfate precipitation and Mono Q chromatography. Activity was assayed as 32P-incorporation into myelin basic protein. Two activity peaks were identified; peak I eluted with approximately 0.1 M NaCl and peak II with approximately 0.2 M NaCl. Three min after insulin injection the activity of peak II increased > 2-fold, peak I was unchanged. After 10 min, the activity of peak II returned toward baseline, while peak I was activated approximately 3-fold. Immunoblots confirmed the presence of MAP kinases eluting with activity peaks I and II; the former as a approximately 41 kDa protein and the latter as a doublet of approximately 42 and approximately 44 kDa. The data suggest sequential activation of two MAP kinases in muscles; the isoform which activates/deactivates rapidly may represent ERK-1, while the more slowly responding isoform may be ERK-2.
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PMID:Sequential activation of two mitogen activated protein (MAP) kinase isoforms in rat skeletal muscle following insulin injection. 826 93

The let-60 ras gene of Caenorhabditis elegans is one of the key players in a signal transduction pathway that controls the choice between vulval and epidermal differentiation in response to extracellular signals. To identify components acting downstream of let-60 ras in the vulval signaling pathway, we have identified a reduction-of-function mutation in the sur-1 gene that completely suppresses the multivulva phenotype of a hyperactive let-60 ras mutation. About 10% of animals homozygous for the sur-1 mutation also display a specific and intriguing vulval cell lineage defect. In addition, the sur-1 mutation results in a cold-sensitive egg-laying defective phenotype and a partial larval lethal phenotype. We have cloned the sur-1 gene by DNA-mediated transformation and have shown that it encodes a protein similar in overall structure to mammalian MAP kinases (ERKs). The functional homology between Sur-1 MAP kinase and mammalian MAP kinases was also demonstrated by the ability of a rat ERK2 kinase to rescue the sur-1 mutant phenotypes. Genetic double-mutant analyses place sur-1 downstream of let-60 ras but upstream of lin-1 in the vulval signaling pathway. Our results provide further evidence for the extreme conservation of Ras-mediated signaling pathway between worms and humans and for the function of MAP kinases in cell signaling processes that control cell differentiation and animal development.
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PMID:Suppression of activated Let-60 ras protein defines a role of Caenorhabditis elegans Sur-1 MAP kinase in vulval differentiation. 829 35

In KB cells, interleukin-1 (IL-1), epidermal growth factor and phorbol ester transiently activated both MAP kinase and a serine kinase which phosphorylated the heat shock protein hsp27. Extracts made from IL-1-stimulated KB cells phosphorylated recombinant hsp27, in vitro, on serine residues 78 and 82 which are contained within Arg-X-X-Ser motifs similar to those phosphorylated by the ribosomal protein S6 kinases. Upon size exclusion chromatography, however, hsp27 kinase eluted as a single peak of activity at 50-60 kDa, clearly separated from ribosomal protein S6 kinases. Treatment of partially purified hsp27 kinase with protein phosphatase-2a reduced its activity by 80%. De-phosphorylated hsp27 kinase could be approximately 50% reactivated by a factor present in IL-1-treated cell extracts in the presence of ATP. This factor co-eluted with MAP kinase after partial purification by DEAE-cellulose, phenyl Sepharose, and size exclusion chromatography. Purified sea star p44mpk and recombinant ERK2 MAP kinases were also capable of re-activating hsp27 kinase to a similar extent. These data suggest that hsp27 kinase is downstream from, and probably a direct target of MAP kinase.
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PMID:The interleukin-1-stimulated protein kinase that phosphorylates heat shock protein hsp27 is activated by MAP kinase. 830 52


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