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.
Mesh Terms:
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
Mol. Cell
Date: Dec. 01, 1999
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