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

---

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

p21ras plays an important role in the control of cell proliferation. The molecular mechanisms implicated are unknown. We report that the injection of oncogenic Lys12 Ras into Xenopus laevis oocytes promoted the activation of mitogen-activated protein kinase (MAP kinase) after a lag of about 90 min. MAP kinase activity was 10-fold higher 4 h after injection of oncogenic Lys12 Ras than after injection of nononcogenic Gly12 Ras. The stimulated MAP kinase activity remained at a plateau for at least 18 h. Maximal stimulation was obtained with 5 ng of Lys12 Ras, which is similar to the amount that elicits germinal vesicle breakdown. DEAE-Sephacel chromatography of extracts from Lys12 Ras-injected oocytes showed one peak of MAP kinase. MAP kinase activation by Lys12 Ras was associated with tyrosine phosphorylation of MAP kinase (p42). As previously shown, the S6-kinase II (likely pp90rsk), which is activated in vitro by MAP kinase, was also activated by oncogenic Lys12 Ras. Lys12 Ras with an additional mutation (Glu38) in the effector region that binds GTPase-activating protein (GAP) did not promote MAP kinase or S6 kinase activations. Thus, GAP may be involved downstream to Ras in these activation processes. Our results indicate that the Ras-GAP complex promotes MAP kinase activation in oocytes. This supports the idea that Ras-GAP controls MAP kinase, a kinase implicated in the action of various stimuli.
...
PMID:Stimulation of mitogen-activated protein kinase by oncogenic Ras p21 in Xenopus oocytes. Requirement for Ras p21-GTPase-activating protein interaction. 132 93

Insulin-induced differentiation of 3T3 L1 cells to adipocytes can be mimicked by the expression of transfected ras oncogenes but not of the tyrosine-kinase oncogenes src and trk. Expression of two different transfected, dominant inhibitory ras mutants resulted in significant inhibition of insulin-induced differentiation, suggesting that endogenous Ras proteins are mediators of insulin signaling in these cells. Exposure of untransfected 3T3 L1 cells to insulin resulted in significant formation of the active Ras.GTP complex, at levels comparable with those resulting from exposure to platelet-derived growth factor. However, whereas exposure of the same cells to platelet-derived growth factor resulted in significant tyrosine phosphorylation of the p21ras GTPase-activating protein (GAP), insulin-treated cells did not show any detectable levels of de novo GAP tyrosine phosphorylation. Interestingly, insulin caused tyrosine phosphorylation of the p62 polypeptide coprecipitated with GAP by anti-GAP antibodies. Insulin-induced activation of cytosolic MAP kinase activity in untransfected 3T3 L1 cells was also mimicked by Ras expression (in the absence of insulin) in the same cells transfected with an inducible ras construct. These results confirm that Ras proteins participate in insulin signaling pathways in these mammalian cells and indicate that activation of cytosolic MAP kinases is an early event occurring downstream from Ras activation. However, tyrosine phosphorylation of GAP appears not to be a significant upstream regulatory event in the activation of Ras by insulin.
...
PMID:Activation of Ras by insulin in 3T3 L1 cells does not involve GTPase-activating protein phosphorylation. 132 23

Both MAP kinases and the protein kinase p74raf-1 are activated by many growth factors in a c-ras-dependent manner and by oncogenic p21ras. We were therefore interested in determining the relationship between MAP kinases and raf. The MAP kinase ERK2 is activated by expression of oncogenically activated raf, independently of cellular ras. Overexpressed p74raf-1 potentiates activation of ERK2 by EGF and TPA. MAP kinase kinase inactivated by phosphatase 2A treatment is phosphorylated and reactivated by incubation with p74raf-1 immunoprecipitated from phorbol ester-treated cells. We conclude that raf protein kinase is upstream of MAP kinases and is either a MAP kinase kinase kinase or a MAP kinase kinase kinase kinase.
...
PMID:Activation of the MAP kinase pathway by the protein kinase raf. 133 Mar 21

To examine signal transduction events activated by oncogenic p21ras, we have studied kinases that are activated following the scrape loading of p21ras into quiescent cells. We observe rapid activation of 42 kDa and 46 kDa protein kinases. The 42 kDa kinase is the mitogen and extracellular-signal regulated kinase ERK2, (MAP2 kinase), which is activated by phosphorylation on tyrosine and threonine in response to oncogenic p21ras, while the 46 kDa kinase is likely to be another member of the ERK family. Stimulation of these kinases by oncogenic p21ras does not require the presence of growth factors, showing that oncogenic p21ras uncouples kinase activation from external signals. In ras transformed cell lines, these kinases are constitutively activated. We propose that the kinases are important components of the signal transduction pathway activated by p21ras oncoprotein.
...
PMID:Activation of extracellular signal-regulated kinase, ERK2, by p21ras oncoprotein. 137 63

Expression of oncogenic ras in PC12 cells causes neuronal differentiation and sustained protein tyrosine phosphorylation and activity of extracellular signal-regulated kinases (ERKs), p42erk2 and p44erk1. Oncogenic N-ras-induced neuronal differentiation is inhibited by compounds that block ERK protein tyrosine phosphorylation or ERK activity, indicating that ERKs are not only activated by p21ras but serve as the primary downstream effectors of p21ras. Treatment of PC12 cells with nerve growth factor or fibroblast growth factor results in neuronal differentiation and in a sustained elevation of p21ras activity, of ERK activity, and of ERK tyrosine phosphorylation. Epidermal growth factor, which does not cause neuronal differentiation, stimulates only transient (< 1 hr) activation of p21ras and ERKs. These data indicate that transient activation of p21ras and, consequently, ERKs is not sufficient for induction of neuronal differentiation. Prolonged ERK activity is required: a consequence of sustained activation of p21ras by the growth factor receptor protein tyrosine kinase.
...
PMID:PC12 cell neuronal differentiation is associated with prolonged p21ras activity and consequent prolonged ERK activity. 138 73

Many growth factors upon stimulation of their receptors induce the activity of extracellular signal-regulated kinases, ERKs, also known as MAP kinases. Several of these growth factors also activate the ras proto-oncogene product, p21ras (Ras), by stimulating the conversion of the inactive GDP-bound form of Ras to the active GTP-bound form. We have shown that direct introduction of p21ras oncoprotein into cells in the absence of growth factors activates ERKs within five minutes, which indicates that normal p21ras may be involved in the activation of ERKs by growth factors. Here we use a recombinant vaccinia virus expressing an interfering mutant of p21ras, RasAsn17, to investigate this question. In NIH3T3 cells that overexpress the insulin receptor, this recombinant virus inhibits insulin-induced activation of ERK2 completely, but there is no inhibition of insulin-induced activation of phosphatidylinositol-3-kinase. In rat-1 cells the recombinant virus inhibited ERK2 activity induced by platelet-derived growth factor (PDGF) but not by phorbol ester. We conclude that p21ras mediates insulin- and PDGF-induced activation of ERK2.
...
PMID:Involvement of p21ras in activation of extracellular signal-regulated kinase 2. 144 47

Apoptosis of haemopoietic cells can be inhibited by various cytokines, but the specific signalling pathways involved are not well defined. Interleukin (IL)-4 has unique actions since it is unable to activate p21ras or mitogen-activated protein kinase, but can activate PtdIns 3-OH-kinase (PtdIns 3-kinase), the latter effect being shared with most other cytokines. In many cases, IL-4 is able to maintain cell viability by inhibiting apoptosis, but is unable to stimulate continuous proliferation of cells. This led us to investigate the role of PtdIns 3-kinase in inhibition of apoptosis. Two potent inhibitors of PtdIns 3-kinase, wortmannin and LY294002, rapidly induced apoptosis in cells incubated in the presence of IL-4, at concentrations consistent with their ability to inhibit PtdIns 3-kinase activity in whole cells. Interestingly, the same effect was seen in cells in the presence of IL-3 and Steel factor, while cells incubated in the presence of granulocyte-macrophage colony stimulating factor, and to a lesser extent, IL-5 could bypass the effect of wortmannin or LY294002. Therefore, this study suggests that PtdIns 3-kinase activity provides an important, although not a unique signal, required to inhibit apoptosis in haemopoietic cells.
...
PMID:Role of phosphatidylinositol 3-OH-kinase activity in the inhibition of apoptosis in haemopoietic cells: phosphatidylinositol 3-OH-kinase inhibitors reveal a difference in signalling between interleukin-3 and granulocyte-macrophage colony stimulating factor. 749 6

Insulin stimulates glucose transport largely by mediating translocation of the insulin-sensitive glucose transporter (GLUT4) from an intracellular compartment to the plasma membrane. Using single cell microinjection of 3T3-L1 adipocytes, coupled with immunofluorescence detection of GLUT4 proteins, we have determined that inhibition of endogenous p21ras or injection of oncogenic p21ras has no effect on insulin-stimulated GLUT4 translocation. On the other hand, microinjection of anti-phosphotyrosine antibodies or inhibition of endogenous phosphatidylinositol 3-kinase by microinjection of a GST-p85 SH2 fusion protein markedly inhibits this biologic effect of insulin. These data suggest that the p21ras/mitogen-activated protein kinase pathway is not involved in this metabolic effect of insulin, whereas tyrosine phosphorylation and stimulation of phosphatidylinositol 3-kinase activity are critical components of this signaling pathway.
...
PMID:Insulin-stimulated GLUT4 translocation is mediated by a divergent intracellular signaling pathway. 749 78

The mechanism by which cAMP inhibits growth factor-induced DNA synthesis in fibroblasts is not understood. Here we show that in Rat-1 fibroblasts, cAMP-raising agents inhibit p21ras-mediated mitogen-activated protein (MAP) kinase activation induced by either epidermal growth factor or lysophosphatidic acid. Under the same conditions, however, epidermal growth factor- or lysophosphatidic acid-induced protein tyrosine phosphorylation, Ca2+ mobilization, and activation of Na+/H+ exchange are not attenuated. In ras-transformed Rat-1 cells, 8-bromo-cAMP rapidly deactivates constitutively active MAP kinase without reducing p21ras.GTP levels; long term 8-bromo-cAMP treatment of these cells leads to growth arrest and reversion of the transformed phenotype. These results show that elevation of intracellular cAMP levels abrogates the p21ras MAP kinase pathway at a step downstream of p21ras activation. This finding provides a molecular basis for the growth-inhibitory action of cAMP in normal and transformed fibroblasts.
...
PMID:cAMP abrogates the p21ras-mitogen-activated protein kinase pathway in fibroblasts. 750 16

Granulocyte colony-stimulating factor (G-CSF) can elicit responses that include proliferation, granulocytic differentiation, and activation of cellular functions in target cells. The biochemical pathways responsible for transduction of these signals from the G-CSF receptor (G-CSFR) have not been defined. In this report, we show that, in murine (NFS-60) and human (OCI-AML 1) myeloid leukemia cell lines and in murine pro-B-lymphocytic cells, BAF/B03, transfected with the murine G-CSFR, proliferative responses to G-CSF are associated with rapid activation of p42 and p44 MAP kinases and p21ras. Truncation of the cytoplasmic portion of the murine G-CSFR at residue 646 but not at residue 739 abolished G-CSF-induced stimulation of cellular proliferation as well as activation of MAP kinase and p21ras in transfected BAF/B03 cells. G-CSF-induced granulocytic differentiation of the murine leukemic cell line 32DC13(G) occurred in the absence of detectable activation of p42 MAP kinase. Nonproliferative responses to G-CSF in the human promyelocytic cell line HL-60 and in human neutrophils were similarly associated with no MAP kinase activation. These results imply that differing cellular effects of G-CSF may be involve the recruitment of differing signal transduction pathways with the p21ras/MAP kinase pathway being limited to proliferative responses.
...
PMID:Proliferative but not nonproliferative responses to granulocyte colony-stimulating factor are associated with rapid activation of the p21ras/MAP kinase signalling pathway. 750 13


1 2 3 4 5 6 7 8 9 10 Next >>

---