The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1.
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.
Kimura
Akiko
A
Department of Medicine, Life Sciences Institute, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-0650, USA.
Mora
Silvia
S
Shigematsu
Satoshi
S
Pessin
Jeffrey E
JE
Saltiel
Alan R
AR
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002384:Catalysis; D051242:Caveolin 1; D022461:Caveolins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D011972:Receptor, Insulin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D014443:Tyrosine; D011972:Receptor, Insulin