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PMID: 11157779 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Genes & development ·Vol. 15 ·No. 2 ·2001-01-15 ·Pages 241-53

Xing L, Venegas AM, Chen A, Garrett-Beal L, Boyce BF, Varmus HE, Schwartzberg PL

Abstract

Mutant src(-/-) mice have osteopetrosis resulting from defective osteoclasts, the cells that resorb bone. However, signaling pathways involving Src family members in osteoclasts remain unclear. We demonstrate that expression of a truncated Src molecule, Src251, lacking the kinase domain, induces osteopetrosis in wild-type and src(+/-) mice and worsens osteopetrosis in src(-/-) mice by a novel mechanism, increased osteoclast apoptosis. Induction of apoptosis by Src251 requires a functional SH2, but not an SH3, domain and is associated with reduced AKT kinase activity. Expression of Src251 dramatically reduces osteoclast survival in response to RANKL/TRANCE/OPGL, providing evidence that Src family kinases are required in vivo for survival signaling pathways downstream from TNF family receptors.

MeSH Terms
Animals Apoptosis Base Sequence Cell Survival Chickens DNA Primers/genetics Mice Mice, Knockout Mice, Transgenic Osteoclasts/pathology Osteopetrosis/genetics,pathology Protein Serine-Threonine Kinases Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-akt Receptors, Tumor Necrosis Factor/genetics,metabolism Signal Transduction src Homology Domains src-Family Kinases/chemistry,genetics,metabolism
Chemicals
DNA Primers Proto-Oncogene Proteins Receptors, Tumor Necrosis Factor src-Family Kinases Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Xing L
Department of Pathology, University of Rochester, Rochester, New York 14627, USA.
Venegas A M
Chen A
Garrett-Beal L
Boyce B F
Varmus H E
Schwartzberg P L
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.840301
Published
2001-01-15
Pages
241-53
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312612
Subset
IM
Grants
NIAMS NIH HHS · R01 AR043510 · United States
NIAMS NIH HHS · AR-43510 · United States
External Links
PubMed source DOI: 10.1101/gad.840301 PMC Full Text View journal details
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