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.
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
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
Science
Date: Dec. 24, 2004
PubMed ID: 15618521
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