Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2

Nature 426：574-579，2003

Place： Room 601

Time： 2004/ 06/ 02  15:00-16:00

Speaker： 吳鳳翎

Commentator： 劉校生 老師

Abstract：

G-protein coupled receptors (GPCRs) are activated after received stimulation such as light or adrenaline. It is necessary for cells to desensitize GPCR quickly to receive another extracellular or environmental signal. G protein coupled receptor kinase 2 (GRK-2) phosphorylate active GPCR results in desensitization and internalization (1). Dysregulation of GRK-2 is associated with high blood pressure and heart failure. Therefore, the function of GRK-2 must be tightly controlled (2).  Previous study showed that Raf kinase inhibitory protein (RKIP) is a physiological inhibitor for GRK-2. RKIP can specific inhibit GPCR phosphorylation, which is mediated by GRK-2. The author found that phosphorylated RKIP could disassociate from Raf-1, which in turn associate with GRK-2 and leads to activation of Raf-MEK-ERK cascade (3). This condition happened after RKIP phosphorylation on serine 153 by Protein kinase C. The mechanism was confirmed in cardiomyocyte, in which β₂ -adrenergic receptor internalization is due to the inhibition of GRK-2 by phosphorylated wild type RKIP but not RKIP^S153A. In addition, RKIP RNAi and antibodies were used to block RKIP activity in cardiomyocytes, and then led to decrease the contractile activity of cardiomyocytes. This regulation between Raf-1 (the survival promoting pathway) and GRK-2 (the inhibitory pathway) is first identified.

References：

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