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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)

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

Extracellular signal-regulated kinases (ERK) 1 and 2 are growth factor- and cytokine-sensitive serine/threonine kinases that are known to phosphorylate microtubule-associated protein 2 and myelin basic protein. The current studies examined whether ERK1 and/or ERK2 was present in T cells and whether they were phosphorylated and activated as a consequence of T cell activation. The data demonstrated that both ERK1 and ERK2 were present in Jurkat cells and peripheral blood T cells. In T cells, ERK2 was more prevalent than ERK1. The concentrations of ERK1 and ERK2 were not altered by stimulating the cells for 16 h with immobilized anti-CD3 mAb or anti-CD3 mAb and phorbol myristate acetate. mAb to CD3 and phorbol myristate acetate stimulated an increase in ERK1 and ERK2 MBP kinase activity. Anti-CD3 mAb triggered an increase their phosphate content which was detectable at 2 min but reached a maximum at 5 min. A portion of the increase in phosphate was caused by an increase in phosphotyrosine. We also examined the rate of ERK2 degradation. ERK2 was stable for up to 36 h, and its degradation was unaffected by the activation state of the cells. The data demonstrate that ERK1 and ERK2 are part of an anti-CD3 mAb-stimulated signal transduction cascade that is downstream of protein kinase C and, therefore, suggest that these kinases play an important role in T cell activation.
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PMID:Extracellular signal-regulated kinases in T cells. Anti-CD3 and 4 beta-phorbol 12-myristate 13-acetate-induced phosphorylation and activation. 153 54

Growth hormone (GH) influences a number of tissue-specific biological activities in diverse cell types. However, little is known about the biochemical pathway by which the signal initiated by GH binding to its cell-surface receptor is transduced. The GH receptor has been reported to be phosphorylated on tyrosine in 3T3-F442A cells, a cell line in which GH promotes differentiation and inhibits mitogen-stimulated growth; however, it is not known whether tyrosine phosphorylation plays a role in GH signal transduction. We report that GH treatment of 3T3-F442A cells resulted in the rapid tyrosine phosphorylation of at least four proteins. These included 42- (pp42) and 45-kDa (pp45) proteins immunologically related to ERK1 (extracellular signal-regulated kinase 1), a member of a family of serine/threonine protein kinases that are phosphorylated on tyrosine in response to mitogens. Prolonged phorbol ester pretreatment attenuated the tyrosine phosphorylation of pp42 and pp45 in platelet-derived growth factor-treated cells, but not in GH-treated cells. Maximal GH-stimulated tyrosine phosphorylation of pp42 and pp45 coincided with peak levels of a 42-kDa renaturable MBP kinase activity in lysates of GH-treated cells resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The observation that multiple cellular proteins are rapidly phosphorylated on tyrosine in response to physiological concentrations of GH suggests that tyrosine phosphorylation plays a role in GH signal transduction. Moreover, the stimulation of tyrosine phosphorylation of ERK-related proteins by GH suggests that mitogens and nonmitogens may employ common phosphotyrosyl proteins in the activation of ultimately distinct cellular programs.
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PMID:Growth hormone stimulates the tyrosine phosphorylation of 42- and 45-kDa ERK-related proteins. 153 56

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

Interleukin 1 (IL1) activated mitogen-activated protein (MAP) kinase kinase in human gingival and foreskin fibroblasts and KB cells. Maximal activity was found in cytosolic extracts made after stimulating cells for 15 min. On anion-exchange chromatography two differently charged forms of MAP kinase kinase were identified, both phosphorylated a kinase-defective mutant MAP kinase, and activated recombinant wild type MAP kinase to phosphorylate MBP. Both were inhibited by an antiserum to recombinant MAP kinase kinase and the less acidic form was identified on Western blotting as an antigen of approximately 43 kDa. Indistinguishable forms were very much more strongly induced by phorbol myristate acetate (PMA). TNF had a similar effect to that of IL1.
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PMID:Interleukin 1 and tumour necrosis factor activate the mitogen-activated protein (MAP) kinase kinase in cultured cells. 769 14

Two cell line models for colon goblet cells expressed 6- to 14-fold elevated levels of the EGF receptor, 3- to 5-fold levels of TGF alpha and 11- to 15-fold levels of amphiregulin compared with 2 cell lines which model colon enterocytic differentiation, suggesting a role for the EGF receptor and its ligands in goblet cell growth control. Two HT29 colon carcinoma sublines were used to model normal goblet cells at different stages of maturation. TGF alpha induced a 2-fold increase in growth of the HD8 subline but inhibited the growth of the more differentiated HD6 subline by 40%. EGF receptors were activated in each line by ligand, but signal transduction varied sharply. Both MAP kinase isoforms, p44 and p42, were markedly activated in HD8 cells for at least 20 min, while only a marginal activation was seen in HD6 cells. In contrast, the more differentiated HD6 cells showed an increase in 105 kDa MBP kinase activity with EGF treatment, while HD8 cells displayed constitutively elevated levels of this kinase. Thus, activated EGF receptors initiated different signalling pathways in model cell lines for colon goblet cells at different stages of maturation. TGF alpha protein levels have been shown by other investigators to be restricted to the top of the cylinder-like colonic crypt, where cells terminally differentiate and cease division, an unexpected location for an epithelial cell mitogen. Our data with model cell lines imply that normal colon goblet cells lose proliferative response to TGF alpha as they differentiate and the elevated levels of TGF alpha at the top of the colonic crypt in vivo serve to inhibit goblet cell growth.
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PMID:Colon goblet cells lose proliferative response to TGF alpha as they differentiate. 779 Jan 21

Previously we have shown that reactive oxygen species (ROS) formation induced by phorbol ester in association with vanadate is essential for protein tyrosine phosphorylation and phospholipase A2 (PLA2) activation. Here we show that the interaction of beta-glucan particles (glucanp) or zymosan with complement receptor type 3 (CR3) leads, when associated with vanadate, to a cascade of reactions culminating in PLA2 activation. Vanadate + zymosan (or glucanp) markedly enhance protein tyrosine phosphorylation in bone marrow derived macrophages (BMMs), whereas neither of the agents alone has any effect. The enhancement was due to both sustained activation of protein tyrosine kinase (PTK) and inactivation of protein tyrosine phosphatase (PTP) as assessed in lysates of treated cells. Zymosan elevates membranal PKC, an effect that is potentiated by vanadate. Activation of both PTK and PKC leads to the activation of NADPH oxidase and to ROS formation. The formed ROS together with vanadate are potent inactivators of PTP leading to amplification of tyrosine phosphorylation and myelin basic protein kinase (MBP-K) activation. The activation of the cascade of protein kinases eventually leads to activation of PLA2. All the activation steps, i.e., activation of PTK, NADPH oxidase, MBP-K,PLA2 and the inactivation of PTP are sensitive to the NADPH oxidase inhibitor diphenyleneiodonium (DPI), to antioxidants and to PKC inhibitors. Thus, ROS formation (in the presence of vanadate) is critical for protein phosphorylation processes constituting the regulatory pathway of PLA2 activation by ligand-CR3 interaction.
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PMID:A role for reactive oxygen species in zymosan and beta-glucan induced protein tyrosine phosphorylation and phospholipase A2 activation in murine macrophages. 803 63

The stimulation of translation in starfish oocytes by the maturation hormone, 1-methyladenine (1-MA), requires the activation or mobilization of both initiation factors and mRNAs [Xu and Hille, Cell Regul. 1:1057, 1990]. We identify here the translational initiation complex, eIF-4F, and the guanine nucleotide exchange factor for eIF-2, eIF-2B, as the rate controlling components of protein synthesis in immature oocytes of the starfish, Pisaster orchraceus. Increased phosphorylation of eIF-4E, the cap binding subunit of the eIF-4F complex, is coincident with the initial increase in translational activity during maturation of these oocytes. Significantly, protein kinase C activity increased during oocyte maturation in parallel with the increase in eIF-4E phosphorylation and protein synthesis. An increase in the activities of cdc2 kinase and mitogen-activated myelin basic protein kinase (MBP kinase) similarly coincide with the increase in eIF-4E phosphorylation. However, neither cdc2 kinase nor MBP kinase phosphorylates eIF-4E in vitro. Casein kinase II activity does not change during oocyte maturation, and therefore, cannot be responsible for the activation of translation. Treatment of oocytes with phorbol 12-myristate 13-acetate, an activator of protein kinase C, for 30 min prior to the addition of 1-MA resulted in the inhibition of 1-MA-induced phosphorylation of eIF-4E, translational activation, and germinal vesicle breakdown. Therefore, protein kinase C may phosphorylate eIF-4E, after very early events of maturation. Another possibility is that eIF-4E is phosphorylated by an unknown kinase that is activated by the cascade of reactions stimulated by 1-MA. In conclusion, our results suggest a role for the phosphorylation of eIF-4E in the activation of translation during maturation, similar to translational regulation during the stimulation of growth in mammalian cells.
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PMID:Maturation hormone induced an increase in the translational activity of starfish oocytes coincident with the phosphorylation of the mRNA cap binding protein, eIF-4E, and the activation of several kinases. 811 71

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


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