Serine 338 Phosphorylation Is Dispensable for Activation of c-Raf1
| Autor: | Ignacio Rubio, Wolf Oehrl, Reinhard Wetzker |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Time Factors
MAP Kinase Signaling System Blotting Western Guanosine Biology Biochemistry Gene Expression Regulation Enzymologic Phosphorylation cascade Serine Phosphatidylinositol 3-Kinases chemistry.chemical_compound Anti-apoptotic Ras signalling cascade Humans Enzyme Inhibitors Phosphorylation Kinase activity Molecular Biology Glutathione Transferase Kinase U937 Cells Cell Biology Genistein Cell biology Androstadienes Enzyme Activation Proto-Oncogene Proteins c-raf chemistry Guanosine 5'-O-(3-Thiotriphosphate) ras Proteins Tyrosine Guanosine Triphosphate Wortmannin Tyrosine kinase Protein Binding Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 278:17819-17826 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m209951200 |
| Popis: | Numerous extracellular agonists induce consecutive stimulation of Ras guanine nucleotide exchange factors, Ras and c-Raf1, as the starting point of the intracellular mitogen-activated protein kinase cascade. Recent data point to a more complex reaction pattern of this simple sequence. This study was aimed at elucidating the activation process of endogenous c-Raf1 in U937 cells. Treatment of permeabilized U937 cells with the nonhydrolyzable nucleotide guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) induced prolonged stimulation of Ras and c-Raf1 activity. Intriguingly, both signaling proteins expressed differential responses toward specific inhibitors of phosphoinositide 3-kinases and tyrosine kinases, which indicates diverse signaling reactions feeding into Ras and cRaf-1. Phosphorylation of c-Raf1 serine 338 by p21-activated kinase has been recently reported to contribute to phosphoinositide 3-kinase-dependent activation of c-Raf1. However, in U937 cells stimulation of c-Raf1 activity by GTPgammaS did not correlate with p21-activated kinase activity and Ser-338 phosphorylation. Thus Ser-338 phosphorylation appears dispensable for c-Raf1 activation under the conditions used. Together these data deny an essential role for serine 338 phosphorylation in c-Raf1 activation and disclose divergent signaling connections of Ras and c-Raf1 in U937 cells. |
| Databáze: | OpenAIRE |
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