TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src.
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 ID: 10635328 RIS Download
Animals | Carrier Proteins | Cells, Cultured | Dendritic Cells | Membrane Glycoproteins | Osteoclasts | Protein-Serine-Threonine Kinases | Protein-Tyrosine Kinases | Proteins | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-akt | RANK Ligand | Receptors, Tumor Necrosis Factor | Signal Transduction | TNF Receptor-Associated Factor 6 | Tumor Necrosis Factor-alpha | src-Family Kinases