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Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1.

The ablation of the protein kinase Raf-1 renders cells hypersensitive to apoptosis despite normal regulation of extracellular signal-regulated kinases, which suggests that apoptosis protection is mediated by a distinct pathway. We used proteomic analysis of Raf-1 signaling complexes to show that Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (MST2). Raf-1 prevents dimerization and phosphorylation of the activation loop of MST2 independently of its protein kinase activity. Depletion of MST2 from Raf-1-/- mouse or human cells abrogated sensitivity to apoptosis, whereas overexpression of MST2 induced apoptosis. Conversely, depletion of Raf-1 from Raf-1+/+ mouse or human cells led to MST2 activation and apoptosis. The concomitant depletion of both Raf-1 and MST2 prevented apoptosis.

Pubmed ID: 15618521


  • O'Neill E
  • Rushworth L
  • Baccarini M
  • Kolch W


Science (New York, N.Y.)

Publication Data

December 24, 2004

Associated Grants


Mesh Terms

  • Animals
  • Antigens, CD95
  • Apoptosis
  • COS Cells
  • Cell Line, Tumor
  • Dimerization
  • Humans
  • Mice
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Proteomics
  • Proto-Oncogene Proteins c-raf
  • RNA, Small Interfering
  • Signal Transduction
  • Staurosporine
  • Transfection