Genetic evidence for a role for Src family kinases in TNF family receptor signaling and cell survival

Citation
Lp. Xing et al., Genetic evidence for a role for Src family kinases in TNF family receptor signaling and cell survival, GENE DEV, 15(2), 2001, pp. 241-253
Citations number
57
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
GENES & DEVELOPMENT
ISSN journal
0890-9369 → ACNP
Volume
15
Issue
2
Year of publication
2001
Pages
241 - 253
Database
ISI
SICI code
0890-9369(20010115)15:2<241:GEFARF>2.0.ZU;2-A
Abstract
Mutant src(-/-) mice have osteopetrosis resulting from defective osteoclast s, the cells that resorb bone. However, signaling pathways involving Src fa mily members in osteoclasts remain unclear. We demonstrate that expression of a truncated Src molecule, Src251, lacking the kinase domain, induces ost eopetrosis in wild-type and src(+/-) mice and worsens osteopetrosis in src( -/-) mice by a novel mechanism, increased osteoclast apoptosis. Induction o f apoptosis by Src251 requires a functional SH2, but not an SH3, domain and is associated with reduced ART kinase activity. Expression of Src251 drama tically reduces osteoclast survival in response to RANKL/TRANCE/OPGL, provi ding evidence that Src family kinases are required in vivo for survival sig naling pathways downstream from TNF family receptors.