Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10

Shian Huey Chiang, Christian A. Baumann, Makoto Kanzaki, Debbie C. Thurmond, Robert T. Watson, Cheryl L. Neudauer, Ian G. Macara, Jeffrey E. Pessin, Alan R. Saltiel

Research output: Contribution to journalArticle

438 Citations (Scopus)

Abstract

The stimulation of glucose uptake by insulin in muscle and adipose tissue requires translocation of the GLUT4 glucose transporter protein from intracellular storage sites to the cell surface. Although the cellular dynamics of GLUT4 vesicle trafficking are well described, the signalling pathways that link the insulin receptor to GLUT4 translocation remain poorly understood. Activation of phosphatidylinositol-3-OH kinase (PI(3)K) is required for this trafficking event, but it is not sufficient to produce GLUT4 translocation. We previously described a pathway involving the insulin-stimulated tyrosine phosphorylation of Cbl, which is recruited to the insulin receptor by the adapter protein CAP. On phosphorylation, Cbl is translocated to lipid rafts. Blocking this step completely inhibits the stimulation of GLUT4 translocation by insulin. Here we show that phosphorylated Cbl recruits the CrkII-C3G complex to lipid rafts, where C3G specifically activates the small GTP-binding protein TC10. This process is independent of PI(3)K, but requires the translocation of Cbl, Crk and C3G to the lipid raft. The activation of TC10 is essential for insulin-stimulated glucose uptake and GLUT4 translocation, The TC10 pathway functions in parallel with PI(3)K to stimulate fully GLUT4 translocation in response to insulin.

Original languageEnglish (US)
Pages (from-to)944-948
Number of pages5
JournalNature
Volume410
Issue number6831
DOIs
StatePublished - Apr 19 2001
Externally publishedYes

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Insulin
Phosphatidylinositol 3-Kinases
Insulin Receptor
Lipids
Phosphorylation
Glucose
Facilitative Glucose Transport Proteins
GTP-Binding Proteins
Tyrosine
Adipose Tissue
Proteins
Muscles

ASJC Scopus subject areas

  • General

Cite this

Chiang, S. H., Baumann, C. A., Kanzaki, M., Thurmond, D. C., Watson, R. T., Neudauer, C. L., ... Saltiel, A. R. (2001). Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature, 410(6831), 944-948. https://doi.org/10.1038/35073608

Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. / Chiang, Shian Huey; Baumann, Christian A.; Kanzaki, Makoto; Thurmond, Debbie C.; Watson, Robert T.; Neudauer, Cheryl L.; Macara, Ian G.; Pessin, Jeffrey E.; Saltiel, Alan R.

In: Nature, Vol. 410, No. 6831, 19.04.2001, p. 944-948.

Research output: Contribution to journalArticle

Chiang, SH, Baumann, CA, Kanzaki, M, Thurmond, DC, Watson, RT, Neudauer, CL, Macara, IG, Pessin, JE & Saltiel, AR 2001, 'Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10', Nature, vol. 410, no. 6831, pp. 944-948. https://doi.org/10.1038/35073608
Chiang SH, Baumann CA, Kanzaki M, Thurmond DC, Watson RT, Neudauer CL et al. Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature. 2001 Apr 19;410(6831):944-948. https://doi.org/10.1038/35073608
Chiang, Shian Huey ; Baumann, Christian A. ; Kanzaki, Makoto ; Thurmond, Debbie C. ; Watson, Robert T. ; Neudauer, Cheryl L. ; Macara, Ian G. ; Pessin, Jeffrey E. ; Saltiel, Alan R. / Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. In: Nature. 2001 ; Vol. 410, No. 6831. pp. 944-948.
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