[HTML][HTML] Kinase suppressor of Ras is ceramide-activated protein kinase

Y Zhang, B Yao, S Delikat, S Bayoumy, XH Lin, S Basu… - Cell, 1997 - cell.com
Y Zhang, B Yao, S Delikat, S Bayoumy, XH Lin, S Basu, M McGinley, PY Chan-Hui…
Cell, 1997cell.com
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 …
Abstract
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.
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