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

Item Type:Article
Title:TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src
Creators Name:Wong, B.R. and Besser, D. and Kim, N. and Arron, J.R. and Vologodskaia, M. and Hanafusa, H. and Choi, Y.
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.
Keywords:Carrier Proteins, Cultured Cells , Dendritic Cells, Membrane Glycoproteins, Osteoclasts, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, RANK Ligand, Tumor Necrosis Factor Receptors, Signal Transduction, TNF Receptor-Associated Factor 6, Tumor Necrosis Factor-alpha, Animals
Source:Molecular Cell
Publisher:Cell Press
Page Range:1041-1049
Date:December 1999
Official Publication:https://doi.org/10.1016/S1097-2765(00)80232-4
PubMed:View item in PubMed

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