| Autor: |
Abraham, Dietmar, Podar, Klaus, Pacher, Margit, Kubicek, Markus, Welzel, Natascha, Hemmings, Brian A., Dilworth, Stephen M., Mischak, Harald, Kolch, Walter, Baccarini, Manuela |
| Zdroj: |
Journal of Biological Chemistry; July 2000, Vol. 275 Issue: 29 p22300-22304, 5p |
| Abstrakt: |
The Raf-1 kinase plays a key role in relaying proliferation signals elicited by mitogens or oncogenes. Raf-1 is regulated by complex and incompletely understood mechanisms including phosphorylation. A number of studies have indicated that phosphorylation of serines 259 and 621 can inhibit the Raf-1 kinase. We show that both serines are hypophosphorylated during early mitogenic stimulation and that hypophosphorylation correlates with peak Raf-1 activation. Concentrations of okadaic acid that selectively inhibit protein phosphatase 2A (PP2A) induce phosphorylation of these residues and prevent maximal activation of the Raf-1 kinase. This effect is mediated via phosphorylation of serine 259. The PP2A core heterodimer forms complexes with Raf-1 in vivoand in vitro. These data identify PP2A as a positive regulator of Raf-1 activation and are the first indication that PP2A may support the activation of an associated kinase. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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