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PMID: 9210408 Published · ppublish English Journal Article

Insulin stimulates tyrosine phosphorylation of the proto-oncogene product of c-Cbl in 3T3-L1 adipocytes.

The Biochemical journal ·Vol. 324 ( Pt 3) ·1997-06-15 ·Pages 839-45

Ribon V, Saltiel AR

Abstract

We report here that the product of the c-Cbl proto-oncogene is prominently tyrosine phosphorylated in response to insulin in 3T3-L1 adipocytes. The tyrosine phosphorylation of c-Cbl reaches a maximum within 1-2 min after stimulation by insulin and gradually declines thereafter. The tyrosine phosphorylation of c-Cbl was also observed after treatment of 3T3-L1 adipocytes with epidermal growth factor, whereas platelet-derived growth factor had no effect. After insulin-dependent tyrosine phosphorylation, c-Cbl specifically associates with fusion proteins containing the Src homology 2 (SH2) domains of Crk and the Fyn tyrosine kinase, but not with fusion proteins containing the SH2 domains of either the p85 subunit of phosphatidylinositol 3'-kinase or the tyrosine phosphatase SHPTP2/Syp. Furthermore insulin stimulates the association of c-Cbl with endogenous c-Crk and Fyn in intact 3T3-L1 adipocytes. The tyrosine phosphorylation of c-Cbl is regulated during adipocyte differentiation. Neither insulin-like growth factor 1 nor insulin stimulated the tyrosine phosphorylation of c-Cbl in 3T3-L1 fibroblasts. Moreover, c-Cbl is not tyrosine phosphorylated in response to insulin in cells expressing high levels of the human insulin receptor, or in hepatocytes, despite comparable levels of c-Cbl expression. These results suggest that c-Cbl might have a novel function in the regulation of insulin receptor intracellular signalling in 3T3-L1 adipocytes.

MeSH Terms
3T3 Cells Adipocytes/drug effects,metabolism Animals Fibroblasts/drug effects,metabolism Humans Insulin/pharmacology Insulin-Like Growth Factor I/pharmacology Mice Phosphorylation Protein Binding Proto-Oncogene Mas Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-cbl Proto-Oncogene Proteins c-crk Proto-Oncogene Proteins c-fyn Tyrosine/metabolism Ubiquitin-Protein Ligases src Homology Domains
Chemicals
Insulin MAS1 protein, human Proto-Oncogene Mas Proto-Oncogene Proteins Proto-Oncogene Proteins c-crk Tyrosine Insulin-Like Growth Factor I Proto-Oncogene Proteins c-cbl Ubiquitin-Protein Ligases FYN protein, human Fyn protein, mouse Proto-Oncogene Proteins c-fyn CBL protein, human Cbl protein, mouse
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ribon V
Department of Physiology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
Saltiel A R
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj3240839
Published
1997-06-15
Pages
839-45
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1218500
Subset
IM
External Links
PubMed source DOI: 10.1042/bj3240839 PMC Full Text View journal details
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