Title

The protein-tyrosine kinase fer associates with signaling complexes containing insulin receptor substrate-1 and phosphatidylinositol 3-kinase

UMMS Affiliation

Program in Molecular Medicine and Department of Biochemistry and Pharmacology

Date

9-28-2000

Document Type

Article

Subjects

1-Phosphatidylinositol 3-Kinase; 3T3 Cells; Adipocytes; Amino Acid Sequence; Animals; COS Cells; Cell Differentiation; Cells, Cultured; DNA, Complementary; Electrophoresis, Polyacrylamide Gel; Gene Library; Immunoblotting; Insulin; Mice; Molecular Sequence Data; Phosphoproteins; Phosphorylation; Platelet-Derived Growth Factor; Precipitin Tests; Protein Binding; Protein Isoforms; Protein Structure, Tertiary; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Recombinant Fusion Proteins; Sequence Homology, Amino Acid; Signal Transduction; Time Factors; Transfection; Tyrosine; src Homology Domains

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

In a screen for 3T3-F442A adipocyte proteins that bind SH2 domains, we isolated a cDNA encoding Fer, a nonreceptor protein-tyrosine kinase of the Fes/Fps family that contains a functional SH2 domain. A truncated splicing variant, iFer, was also cloned. iFer is devoid of both the tyrosine kinase domain and a functional SH2 domain but displays a unique 42-residue C terminus and retains the ability to form oligomers with Fer. Expression of both Fer and iFer proteins are strikingly increased upon differentiation of 3T3-L1 fibroblasts to adipocytes. Platelet-derived growth factor treatment of the cultured adipocytes caused rapid tyrosine phosphorylation of Fer and its recruitment to complexes containing platelet-derived growth factor receptor and the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase. Insulin treatment of 3T3-L1 adipocytes stimulated association of Fer with complexes containing tyrosine phosphorylated IRS-1 and PI 3-kinase but did not stimulate tyrosine phosphorylation of Fer. PI 3-kinase activity in anti-Fer immunoprecipitates was also acutely activated by insulin treatment of cultured adipocytes. These data demonstrate the presence of Fer tyrosine kinase in insulin signaling complexes, suggesting a role of Fer in insulin action.

Rights and Permissions

Citation: J Biol Chem. 2000 Dec 15;275(50):38995-9000. Link to article on publisher's site

DOI of Published Version

10.1074/jbc.M006665200

Related Resources

Link to Article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

11006284