Kinase suppressor of Ras is ceramide-activated protein kinase Academic Article uri icon

Overview

MeSH Major

  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Signal Transduction
  • ras Proteins

abstract

  • A proline-directed serine/threonine ceramide-activated protein (CAP) kinase mediates transmembrane signaling through the sphingomyelin pathway. CAP kinase reportedly initiates proinflammatory TNF alpha 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. TNF alpha 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, Thr269 the Raf-1 site phosphorylated by CAP kinase, is also recognized by KSR. Thus, by previously established criteria, KSR appears to be CAP kinase.

publication date

  • April 4, 1997

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 9094715

Additional Document Info

start page

  • 63

end page

  • 72

volume

  • 89

number

  • 1