The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1.

Akiko Kimura, Silvia Mora, Satoshi Shigematsu, Jeffrey E. Pessin, Alan R. Saltiel

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Our previous studies revealed that insulin stimulates the tyrosine phosphorylation of caveolin in 3T3L1 adipocytes. To explore the mechanisms involved in this event, we evaluated the association of the insulin receptor with caveolin. The receptor was detected in a Triton-insoluble low density fraction, co-sedimenting with caveolin and flotillin on sucrose density gradients. We also detected the receptor in caveolin-enriched rosette structures by immunohistochemical analysis of plasma membrane sheets from 3T3L1 adipocytes. Insulin stimulated the phosphorylation of caveolin-1 on Tyr(14). This effect of the hormone was not blocked by overexpression of mutant forms of the Cbl-associated protein that block the translocation of phospho-Cbl to the caveolin-enriched, lipid raft microdomains. Moreover, this phosphorylation event was also unaffected by inhibitors of the MAPK and phosphatidylinositol 3-kinase pathways. Although previous studies demonstrated that the Src family kinase Fyn was highly enriched in caveolae, an inhibitor of this kinase had no effect on insulin-stimulated caveolin phosphorylation. Interestingly, overexpression of a mutant form of caveolin that failed to interact with the insulin receptor did not undergo phosphorylation. Taken together, these data indicate that the insulin receptor directly catalyzes the tyrosine phosphorylation of caveolin.

Original languageEnglish (US)
Pages (from-to)30153-30158
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number33
StatePublished - Aug 16 2002
Externally publishedYes

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Caveolins
Caveolin 1
Phosphorylation
Insulin Receptor
Tyrosine
Insulin
Adipocytes
Phosphatidylinositol 3-Kinase
Caveolae
src-Family Kinases
Protein Transport
Cell membranes
Sucrose
Phosphotransferases
Cell Membrane
Association reactions
Hormones
Lipids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Kimura, A., Mora, S., Shigematsu, S., Pessin, J. E., & Saltiel, A. R. (2002). The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1. Journal of Biological Chemistry, 277(33), 30153-30158.

The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1. / Kimura, Akiko; Mora, Silvia; Shigematsu, Satoshi; Pessin, Jeffrey E.; Saltiel, Alan R.

In: Journal of Biological Chemistry, Vol. 277, No. 33, 16.08.2002, p. 30153-30158.

Research output: Contribution to journalArticle

Kimura, A, Mora, S, Shigematsu, S, Pessin, JE & Saltiel, AR 2002, 'The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1.', Journal of Biological Chemistry, vol. 277, no. 33, pp. 30153-30158.
Kimura A, Mora S, Shigematsu S, Pessin JE, Saltiel AR. The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1. Journal of Biological Chemistry. 2002 Aug 16;277(33):30153-30158.
Kimura, Akiko ; Mora, Silvia ; Shigematsu, Satoshi ; Pessin, Jeffrey E. ; Saltiel, Alan R. / The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 33. pp. 30153-30158.
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