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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)

Clam oocytes are arrested naturally at the G2/M border in meiosis and contain an inactive 42 kDa ERK/MAP kinase, p42MAPK. Following fertilization, p42MAPK is rapidly phosphorylated on tyrosine residues and concomitantly activated. Both tyrosine phosphorylation and activation of p42MAPK begin within 2-3 min of fertilization, peak at approximately 15 min, then rapidly decline and disappear around the end of meiosis I. Neither the tyrosine phosphorylated form of p42MAPK nor p42MAPK activity reappears during meiosis II or the succeeding mitotic cell cycles. High doses of molybdate, a potent PTPase inhibitor, block the phosphorylation of p42MAPK and entry into the cell cycle. Lower doses of molybdate delay both p42MAPK phosphorylation and the release from cell cycle arrest, but once cells have re-entered the cell cycle, they continue with near-normal timing. These results argue that the transient activation of p42MAPK at fertilization is a one-time event linked to release from cell cycle arrest. In trying to reconcile this one-time activation of p42MAPK in clam embryos with the recurring, M-phase specific activation of MBP/MAP kinases reported in other systems, we show that cdc2 kinase contributes a major portion of the MBP kinase activity in mitotic extracts. Furthermore, a small fraction of p42MAPK and other related kinases are present in p13suc1-bound material, cautioning against the use of p13suc1 beads for experiments where, in addition to cdc2, the unaccounted presence of other kinase activities could be misleading.
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PMID:Activation of p42 MAP kinase and the release of oocytes from cell cycle arrest. 132 52

We have approached the functioning of a MAP kinase, which is thought to be a "switch kinase" in the phosphorylation cascade initiated from various receptor tyrosine kinases including the insulin receptor. To do so, antipeptide antibodies were raised against the C-terminal portion of ERK1 (extracellular signal-regulated kinase 1), a protein kinase belonging to the family of MAP kinases. With these antipeptide antibodies, we observed the following: (i) a 44-kDa protein can be specifically recognized both under native and denaturing conditions; (ii) a 44-kDa phosphoprotein can be revealed in 32P-labeled cells; its phosphorylation is stimulated by insulin, sodium orthovanadate, and okadaic acid; (iii) a MBP kinase activity can be precipitated, which phosphorylates MBP on threonine residues, and which is stimulated by insulin, sodium orthovanadate, okadaic acid, and fetal calf serum; (iv) this MBP kinase activity appears to be correlated with the in vivo induced phosphorylation of the 44-kDa protein. We next studied the in vitro phosphorylation of this 44-kDa/ERK1-immunoreactive protein. A time- and manganese-dependent phosphorylation was stimulated by the in vitro addition of sodium orthovanadate. Phosphoamino acid analysis of the in vitro phosphorylated 44-kDa protein revealed both threonine and tyrosine phosphorylation. Importantly, this in vitro phosphorylation of MAP kinase results in activation of phosphorylation of added MBP substrate. As a whole, our data indicate that the 44-kDa phosphoprotein identified by our antipeptide antibodies very likely corresponds to a MAP kinase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tyrosine and threonine phosphorylation of an immunoaffinity-purified 44-kDa MAP kinase. 171 57

The mouse protein mSos1 has a central Ras guanine nucleotide exchange domain, and a long proline-rich C-terminal tail which contains several potential binding sites for the SH3 domains of the adaptor protein, Grb2. In fibroblasts, growth factor stimulation results in the recruitment of Grb2-mSos1 into complexes with activated receptors and cytoplasmic phosphoproteins such as Shc, which are apparently involved in Ras activation, and subsequently to an increase in mSos1 phosphorylation on serine and threonine. The catalytic and C-terminal domains of mSos1 contain several potential sites for phosphorylation by mitogen-activated protein kinases. In vitro, purified p42/p44 MAP-kinase selectively phosphorylated the C-terminal tail of mSos1. Comparative tryptic phosphopeptide mapping of mSos1 phosphorylated in vitro by MAP kinase and of mSos1 immunoprecipitated from EGF-stimulated cells, revealed several phosphopeptides in common. These common phosphorylation sites have been mapped to a region encompassing the first three proline (pro)-rich motifs in the tail of mSos1. Furthermore, a region of mSos1 containing the first two pro-rich motifs could associate with MBP kinase activity in vitro. Phosphorylation of mSos1 did not affect binding of Grb2 to mSos1, but appeared to decrease binding of the mSos1-Grb2 complex to Shc and the EGF-receptor. These findings suggest a potential inhibitory role for MAP-kinase in attenuating nucleotide exchange on Ras, by uncoupling mSos1 from membrane-bound receptor complexes that lead to Ras activation.
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PMID:MAP kinase phosphorylation of mSos1 promotes dissociation of mSos1-Shc and mSos1-EGF receptor complexes. 747 66

Prostaglandin H2 (PGH2) and thromboxane A2 (TXA2) are potent activators of platelets and vascular smooth muscle whose responses are mediated through a common G-protein coupled receptor (TXA2/PGH2 receptor). Despite the many studies describing their ability to aggregate platelets and contract vascular smooth muscle, little is known concerning the potential mitogenic capabilities of these autocoids. Mitogen-activated protein kinases (MAP kinases) and ribosomal S6 kinases are well characterized intracellular mediators involved in proliferation of cells. The present study was designed to examine the activation of MAP kinase and S6 kinase in guinea pig coronary artery smooth muscle cells (CASMC) in response to stimulation by a TXA2/PGH2 mimetic, I-BOP ([1S-(1 alpha,2 beta(5Z),3 alpha(1E,3R*),4 alpha)]-7-[3-(3-hydroxy-4-(4'- iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptan-2-yl]-5-h eptenoic acid). Equilibrium radioligand binding assays using [125I]BOP defined a single class of high affinity TXA2/PGH2 receptors on monolayers of guinea pig CASMC (Kd = 0.18 +/- 0.03 nM; 26,476 +/- 3,600 sites/cell; 0.08 +/- 0.01 pmol/mg of protein; n = 12). I-BOP produced a concentration-dependent increase in [3H]thymidine incorporation in these cells (EC50 = 0.3 nM) which was inhibited by a series of TXA2/PGH2 receptor antagonists as well as by verapamil and staurosporine. I-BOP also produced a time-dependent increase in the activation of kinases phosphorylating myelin basic protein (MBP; a substrate for MAP kinase) and RRLSSLRA (S6 peptide; a substrate for pp85rsk kinase), reaching a peak activation between 5 and 10 min. Stimulated MBP kinases were identified as ERK1 and ERK2. The activation of these kinases by I-BOP was inhibited by the TXA2/PGH2 receptor antagonist SQ29548 and also by staurosporine. These results indicate that I-BOP, a TXA2/PGH2 mimetic, produces growth of coronary artery vascular smooth muscle cells, which is preceded by activation of MAP kinase and S6 kinase.
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PMID:Thromboxane A2/prostaglandin H2-stimulated mitogenesis of coronary artery smooth muscle cells involves activation of mitogen-activated protein kinase and S6 kinase. 811 6

1. Phosphorylation of caldesmon was assayed in canine colonic circular smooth muscle strips labelled with 32P and stimulated with 10 microM acetylcholine. Caldesmon was isolated by two-dimensional non-equilibrium pH gel electrophoresis. Stimulation with acetylcholine increased caldesmon phosphorylation significantly from a basal level of 0.6 +/- 0.07 to 1.1 +/- 0.15 mol P1 (mol caldesmon)-1 after 2 min. 2. MAP kinase activities were measured in SDS extracts of muscle by a gel reconstitution method using myelin basic protein. Myelin basic protein kinase activities were observed at 38, 44, 50 and 57 kDa by the gel reconstitution method. Endogenous caldesmon kinase activities were also identified by the gel reconstitution method at 38, 44 and 50 kDa. The 38 and 44 kDa kinases comigrated with proteins labelled by anti-ERK1 MAP kinase antibodies on Western blots. Both 38 and 44 kDa MBP kinase activities increased significantly during contractions induced by 10 microM acetylcholine, 0.1 microM neurokinin A and 70 mM potassium. 3. Phorbol dibutyrate (0.1 microM) potentiated activation of MAP kinases and contraction of depolarized muscles while producing a decrease in fura-2 fluorescence ratio. This suggests that protein kinase C activation is coupled to MAP kinase activity in colonic smooth muscle. 4. MAP kinases isolated form muscle homogenates by Mono Q chromatography were assayed using the specific MAP kinase substrate peptide APRTPGGRR. Stimulation of muscles for 2 min with 10 microM acetylcholine activated both ERK1 and ERK2 MAP kinase activities 2-fold. 5. To determine the effects of caldesmon phosphorylation by MAP kinase on the cross-bridge cycle, actin sliding velocity was measured with an in vitro motility assay. Unphosphorylated turkey gizzard caldesmon (3 microM) significantly reduced mean sliding velocity. Phosphorylation of caldesmon with sea star ERK1 MAP kinase reversed the inhibitory effect of caldesmon on sliding velocity. The results are consistent with a protein kinase cascade being activated by contractile agonists in gastrointestinal smooth muscle which activates ERK MAP kinases leading to phosphorylation of caldesmon. Phosphorylation of caldesmon in vivo may reverse inhibitory influences of caldesmon on cross-bridge cycling.
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PMID:Activation of MAP kinases and phosphorylation of caldesmon in canine colonic smooth muscle. 888 69

We have identified a third member of the p38 group of MAP kinase termed p38 gamma. The cDNA for this MAP kinase encodes an 367 amino acid polypeptide that is slightly greater than 60% identical to p38 and p38 beta. Expression of its mRNA is primarily in muscle with no detectable expression in Northern blots using RNA from other tissues. In contrast to p38 and p38 beta, p38 gamma, fails to phosphorylate ATF-2 or MAPKAP kinase 2 but does like other MAP kinases phosphorylate MBP. In vivo kinase assays using protein extracts from skeletal muscle reveal that a 7-kDa protein is phosphorylated by p38 gamma but not by other members of this group of kinases. We suggest p38 gamma may have unique functions when compared with other members of the p38 group due to its restricted tissue expression and apparent substrate preferences.
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PMID:The primary structure of p38 gamma: a new member of p38 group of MAP kinases. 892 Sep 15

A novel homologue of p38 MAP kinase, called SAPK4, has been cloned which shares 61% amino acid identity with p38 and is expressed predominantly in testes, pancreas and small intestine. We also cloned an alternative form of p38beta, termed p38beta2, which lacks the additional 8 amino acid insertion unique to p38beta. p38, p38beta, p38beta2, ERK6/p38gamma/SAPK3, and SAPK4 were characterized with respect to stimulus-dependent activation in transfected cells, substrate specificity, and sensitivity to inhibition by pyridinyl imidazoles. All homologues were stimulated, although to differing extents, by IL-1beta, TNF, sorbitol, and UV. Only SAPK3 and SAPK4 were stimulated significantly by PMA. p38beta showed the weakest activation overall. MBP, ATF-2, and both MAPKAP kinase-2 and kinase-3 were good substrates of p38 and p38beta in vitro. In contrast, only MBP, ATF2, and MAPKAP kinase-3 proved to be significant substrates of SAPK3 and SAPK4, and of these three, MAPKAP kinase-3 was by far the weakest. p38beta had very poor kinase activity for all substrates except MBP. While both p38 and p38beta2 were comparably inhibited by SB 203580 and SB 202190, neither SAPK3 nor SAPK4 were inhibited. p38beta was partially inhibited by both inhibitors. These data suggest that SAPK3 and SAPK4 form a distinct subset of the p38 MAP kinases with different expression pattern, response to stimuli, substrate specificity, and inhibitor sensitivity.
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PMID:Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles. 920 91

A MBP kinase activity increases at mitosis during the first two embryonic cell cycles of the sea urchin embryo. The activity profile of the MBP kinase is the same both in whole cell extracts and after immunoprecipitation with an anti-MAP kinase antibody (2199). An in-gel assay of MBP activity also shows the same activity profile. The activity is associated with the 44 kDa protein that cross-reacts with anti-MAP kinase antibodies. The 44 kDa protein shows cross-reactivity to anti-phosphotyrosine and MAP kinase-directed anti-phosphotyrosine/phosphothreonine antibodies at the times that MBP kinase activity is high. The 2199 antibody co-precipitates some histone H1 kinase activity, but the MBP kinase activity cannot be accounted for by histone H1 kinase-dependent phosphorylation of MBP. The MAP kinase 2199 antibody was used to purify the MBP kinase activity. Peptide sequencing after partial digestion shows the protein to be homologous to MAP kinases from other species. These data demonstrate that MAP kinase activation during nuclear division is not confined to meiosis, but also occurs during mitotic cell cycles. MAP kinase activity in immunoprecipitates also increases immediately after fertilization, which in the sea urchin egg occurs at interphase of the cell cycle. Treating unfertilized eggs with the calcium ionophore A23187 stimulates the increase in MAP kinase activity, demonstrating that a calcium signal can activate MAP kinase and suggesting that the activation of MAP kinase at fertilization is due to the fertilization-induced increase in cytoplasmic free calcium concentration. This signalling pathway must differ from the pathway responsible for calcium-induced inactivation of MAP kinase activity that is found in eggs that are fertilized in meiotic metaphase.
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PMID:MAP kinase activity increases during mitosis in early sea urchin embryos. 970 49

Cyclic AMP is involved in the differentiation of oligodendrocyte and Schwann cell progenitors into mature myelin producing cells. The involvement of MAP kinases in this pathway was investigated in the D6P2T cell line. This cell line can be induced to display a differentiated phenotype characterized by myelin basic protein gene expression by increased cyclic AMP. Blocking MAP kinase activity with inhibitors of the activating kinase, MEK, by expression of a dominant negative MAP kinase or by expression of the MAP kinase inactivating phosphatase Mkp-1 all blocked the activation of the myelin basic protein promoter in D6P2T cells. In addition, blocking MAP kinase activation during differentiation of an oligodendrocyte-like cell line, CG4, also leads to inhibition of MBP expression. These findings suggest a role for MAP kinase in the cyclic AMP stimulated expression of the myelin basic protein gene during differentiation.
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PMID:Involvement of MAP kinase in the cyclic AMP induction of myelin basic protein gene expression. 982 68

MAPK(Mitogen-activated protein kinase) pathways play an important role in morphorgenesis of Candida albicans. According to the conserved amino acid sequence of the known MAPKs, two degenerate primers attaching to subdomain VIB and IX were designed to screen novel MAPKs in C. albicans. The PCR was performed under non-strigent conditons. 100 PCR fragments were sequenced and among 25 novel gene fragments, two novel MAPK gene fragments were obtained. Using these two PCR fragments as probes to screen a Candida albicans genomic DNA library, two novel MAPK genes designated CSK1(Candida albicans sporulation-related MAP kinase1) and CEK2(Candida albicans extracellular signal-regulated kinase 2) were cloned. These two genes share high similarity with three cloned MAPK genes CEK1 and MKC1 and CaHOG1. The CSK1 gene is 1 193 bp in length, containing a 92 bp intron, coding for a 367 aa protein. The CSK1 shares highest similarity with SMK1, with homology 55.3% in nucleotide sequence and 50% in amino acid sequence. SMK1 encodes a MAPK involved in the sporulation pathway in S. cerevisiae. In vitro kinase activity assay showed that the Csk1 kinase exhibited a phosphorylation ability when using MBP as a substrate but not histone H1.
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PMID:Molecular Cloning of MAPK Gene Family Using Degenerate PCR. 1207 60


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