The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport

Jun Liu, Stephanie M. DeYoung, Joseph B. Hwang, Erin E. O'Leary, Alan R. Saltiel

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Previous studies suggest that the stimulation of glucose transport by insulin involves the tyrosine phosphorylation of c-Cbl and the translocation of the c-Cbl/CAP complex to lipid raft subdomains of the plasma membrane. We now demonstrate that Cbl-b also undergoes tyrosine phosphorylation and membrane translocation in response to insulin in 3T3-L1 adipocytes. Ectopic expression of APS facilitated insulin-stimulated phosphorylation of tyrosines 665 and 709 in Cbl-b. The phosphorylation of APS produced by insulin drove the translocation of both c-Cbl and Cbl-b to the plasma membrane. Like c-Cbl, Cbl-b associates constitutively with CAP and interacts with Crk upon insulin stimulation. Cbl proteins formed homo- and heterodimers in vivo, which required the participation of a conserved leucine zipper domain. A Cbl mutant incapable of dimerization failed to interact with APS and to undergo tyrosine phosphorylation in response to insulin, indicating an essential role of Cbl dimerization in these processes. Thus, both c-Cbl and Cbl-b can initiate a phosphatidylinositol 3-kinase/protein kinase B-independent signaling pathway critical to insulin-stimulated GLUT4 translocation.

Original languageEnglish (US)
Pages (from-to)36754-36762
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number38
DOIs
StatePublished - Sep 19 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Liu, J., DeYoung, S. M., Hwang, J. B., O'Leary, E. E., & Saltiel, A. R. (2003). The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport. Journal of Biological Chemistry, 278(38), 36754-36762. https://doi.org/10.1074/jbc.M300664200