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

Overview

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.

publication date

  • January 15, 2001

Research

keywords

  • Protein Serine-Threonine Kinases
  • Receptors, Tumor Necrosis Factor
  • src-Family Kinases

Identity

PubMed Central ID

  • PMC312612

Scopus Document Identifier

  • 0035862994

Digital Object Identifier (DOI)

  • 10.1101/gad.840301

PubMed ID

  • 11157779

Additional Document Info

volume

  • 15

issue

  • 2