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Mol Cell. 1999 Dec;4(6):1041-9.

TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src.

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  • 1Laboratory of Immunology, Rockefeller University, New York, New York 10021, USA.

Abstract

TRANCE, a TNF family member, and its receptor, TRANCE-R, are critical regulators of dendritic cell and osteoclast function. Here, we demonstrate that TRANCE activates the antiapoptotic serine/threonine kinase Akt/PKB through a signaling complex involving c-Src and TRAF6. A deficiency in c-Src or addition of Src family kinase inhibitors blocks TRANCE-mediated PKB activation in osteoclasts. c-Src and TRAF6 interact with each other and with TRANCE-R upon receptor engagement. TRAF6, in turn, enhances the kinase activity of c-Src leading to tyrosine phosphorylation of downstream signaling molecules such as c-Cbl. These results define a mechanism by which TRANCE activates Src family kinases and PKB and provide evidence of cross-talk between TRAF proteins and Src family kinases.

PMID:
10635328
[PubMed - indexed for MEDLINE]
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