rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
5705
|
pubmed:dateCreated |
2004-12-24
|
pubmed:abstractText |
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:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Dec
|
pubmed:issn |
1095-9203
|
pubmed:author |
|
pubmed:issnType |
Electronic
|
pubmed:day |
24
|
pubmed:volume |
306
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
2267-70
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:15618521-Animals,
pubmed-meshheading:15618521-Antigens, CD95,
pubmed-meshheading:15618521-Apoptosis,
pubmed-meshheading:15618521-COS Cells,
pubmed-meshheading:15618521-Cell Line, Tumor,
pubmed-meshheading:15618521-Dimerization,
pubmed-meshheading:15618521-Humans,
pubmed-meshheading:15618521-Mice,
pubmed-meshheading:15618521-Phosphorylation,
pubmed-meshheading:15618521-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15618521-Proteomics,
pubmed-meshheading:15618521-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:15618521-RNA, Small Interfering,
pubmed-meshheading:15618521-Signal Transduction,
pubmed-meshheading:15618521-Staurosporine,
pubmed-meshheading:15618521-Transfection
|
pubmed:year |
2004
|
pubmed:articleTitle |
Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1.
|
pubmed:affiliation |
The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|