A Positive Regulatory Role for Cbl Family Proteins in Tumor Necrosis Factor-related Activation-induced Cytokine (TRANCE) and CD40L-mediated Akt Activation

Joseph R. Arron, Masha Vologodskaia, Brian R. Wong, Mayumi Naramura, Nacksung Kim, Hua Gu, Yongwon Choi

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) is a TNF family member essential for osteoclast differentiation, and it induces the activation and survival of osteoclasts and mature dendritic cells. We recently demonstrated that TRANCE activates Akt via a mechanism involving TRANCE receptor (TRANCE-R)/RANK, TRAF6, and c-Src. Here, we show that TRANCE-R and CD40 recruit TRAF6, Cbl family-scaffolding proteins, and the phospholipid kinase phosphatidylinositol 3-kinase in a ligand-dependent manner. The recruitment of Cbl-b and c-Cbl to TRANCE-R is dependent upon the activity of Src-family kinases. TRANCE and CD40L-mediated Akt activation is defective in Cbl-b -/- dendritic cells, and CD40L-mediated Akt activation is defective in c-Cbl -/- B cells. These findings implicate Cbl family proteins as not only negative regulators of signaling but as positive modulators of TNF receptor superfamily signaling as well.

Original languageEnglish (US)
Pages (from-to)30011-30017
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number32
DOIs
StatePublished - Aug 10 2001

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RANK Ligand
CD40 Ligand
Chemical activation
TNF Receptor-Associated Factor 6
Cytokines
Osteoclasts
Dendritic Cells
Proteins
Phosphatidylinositol 3-Kinase
Cytokine Receptors
src-Family Kinases
Tumor Necrosis Factor Receptors
Protein Kinases
Phospholipids
B-Lymphocytes
Tumor Necrosis Factor-alpha
Ligands
Modulators
Thermodynamic properties
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A Positive Regulatory Role for Cbl Family Proteins in Tumor Necrosis Factor-related Activation-induced Cytokine (TRANCE) and CD40L-mediated Akt Activation. / Arron, Joseph R.; Vologodskaia, Masha; Wong, Brian R.; Naramura, Mayumi; Kim, Nacksung; Gu, Hua; Choi, Yongwon.

In: Journal of Biological Chemistry, Vol. 276, No. 32, 10.08.2001, p. 30011-30017.

Research output: Contribution to journalArticle

Arron, Joseph R. ; Vologodskaia, Masha ; Wong, Brian R. ; Naramura, Mayumi ; Kim, Nacksung ; Gu, Hua ; Choi, Yongwon. / A Positive Regulatory Role for Cbl Family Proteins in Tumor Necrosis Factor-related Activation-induced Cytokine (TRANCE) and CD40L-mediated Akt Activation. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 32. pp. 30011-30017.
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