APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes

Jun D Liu, Akiko Kimura, Christian A. Baumann, Alan R. Saltiel

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

APS is a Cbl-binding protein that is tyrosine phosphorylated by the insulin receptor kinase. Insulin-stimulated phosphorylation of tyrosine 618 in APS is necessary for its association with c-Cbl and the subsequent tyrosine phosphorylation of Cbl by the insulin receptor in both 3T3-L1 adipocytes and CHO-IR cells. When overexpressed in these cells, wild-type APS but not an APS/Y618F mutant facilitated the tyrosine phosphorylation of coexpressed Cbl and its association with Crk upon insulin stimulation. APS-facilitated phosphorylation occurred on tyrosines 371, 700, and 774 in the Cbl protein. APS also interacted directly with the c-Cbl-associated protein (CAP) and colocalized with the protein in cells. The association was dependent on the SH3 domains of CAP and was independent of insulin treatment. Overexpression of the APS/Y618F mutant in 3T3-L1 adipocytes blocked the insulin-stimulated tyrosine phosphorylation of endogenous Cbl and binding to Crk. Moreover, the translocation of GLUT4 from intracellular vesicles to the plasma membrane was also inhibited by overexpression of the APS/Y618F mutant. These data suggest that APS serves as an adapter protein linking the CAP/Cbl pathway to the insulin receptor and, further, that APS-facilitated Cbl tyrosine phosphorylation catalyzed by the insulin receptor is a crucial event in the stimulation of glucose transport by insulin.

Original languageEnglish (US)
Pages (from-to)3599-3609
Number of pages11
JournalMolecular and Cellular Biology
Volume22
Issue number11
DOIs
StatePublished - 2002
Externally publishedYes

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Adipocytes
Tyrosine
Phosphorylation
Insulin
Insulin Receptor
Proteins
src Homology Domains
CHO Cells
Carrier Proteins
Cell Membrane
Glucose
ponsin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes. / Liu, Jun D; Kimura, Akiko; Baumann, Christian A.; Saltiel, Alan R.

In: Molecular and Cellular Biology, Vol. 22, No. 11, 2002, p. 3599-3609.

Research output: Contribution to journalArticle

Liu, Jun D ; Kimura, Akiko ; Baumann, Christian A. ; Saltiel, Alan R. / APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes. In: Molecular and Cellular Biology. 2002 ; Vol. 22, No. 11. pp. 3599-3609.
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