The BioGRID | PUBLICATION VIEW

	Mol. Cell Dec (1999); 4(6):1041-9
TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src.
Wong BR, Besser D, Kim N, Arron JR, Vologodskaia M, Hanafusa H, Choi Y
Laboratory 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.
[PUBMED: 10635328]