Kinase Suppressor of Ras Is Ceramide-Activated Protein Kinase

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• 作者：Yuhua Zhang ; Bei Yao ; Sylvie Delikat ; Shariff Bayoumy ; Xin-Hua Lin ; Subham Basu ; Michael McGinley ; Po-Ying Chan-Hui ; Henri Lichenstein ; Richard Kolesnick
• 刊名：Cell
• 出版年：1997
• 出版时间：4 April 1997
• 年：1997
• 卷：89
• 期：1
• 页码：63-72
• 全文大小：220 K

文摘

A proline-directed serine/threonine ceramide-activated protein (CAP) kinase mediates transmembrane signaling through the sphingomyelin pathway. CAP kinase reportedly initiates proinflammatory TNFα action by phosphorylating and activating Raf-1. The present studies delineate kinase suppressor of Ras (KSR), identified genetically in Caenorhabditis elegans and Drosophila, as CAP kinase. Mouse KSR, like CAP kinase, renatures and autophosphorylates as a 100-kDa membrane-bound polypeptide. KSR overexpression constitutively activates Raf-1. TNFα or ceramide analogs markedly enhance KSR autophosphorylation and its ability to complex with, phosphorylate, and activate Raf-1. In vitro, low nanomolar concentrations of natural ceramide stimulate KSR to autophosphorylate, and transactivate Raf-1. Other lipid second messengers were ineffective. Moreover, Thr ²⁶⁹, the Raf-1 site phosphorylated by CAP kinase, is also recognized by KSR. Thus, by previously established criteria, KSR appears to be CAP kinase.