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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

Authors

  • Wong BR
  • Besser D
  • Kim N
  • Arron JR
  • Vologodskaia M
  • Hanafusa H
  • Choi Y

Journal

Molecular cell

Publication Data

December 31, 1999

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI-44264
  • Agency: NCI NIH HHS, Id: CA-44356
  • Agency: NIGMS NIH HHS, Id: GM-07739

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
  • src-Family Kinases