This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by BURANT, C. F. Articles by BUSE, M. G. Search for Related Content PubMed PubMed Citation Articles by BURANT, C. F. Articles by BUSE, M. G.

Tissue Specific Differences in the Insulin Receptor Kinase Activated in Vitro and in Vivo^*

CHARLES F. BURANT, MARY K. TREUTELAAR and MARIA G. BUSE

Departments of Medicine and Biochemistry, Medical University of South Carolina Charleston, South Carolina 29425

Address all correspondence and requests for reprints to: Maria G. Buse, M.D., Department of Medicine and Biochemistry, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425.

Abstract

We have recently described structural differences between insulin receptors isolated from rat skeletal muscle and liver. In this report we compared their intrinsic kinase activity and their precipitability with antiphosphotyrosine and polyclonal anti-β-subunit antibodies before and after stimulation by insulin in vitro or in vivo. Liver derived receptors incubated with insulin showed 40–50% less autophosphorylation and exogenous substrate tyrosine kinase activity per insulin binding site than those from muscle, as well as a 50% reduction in the proportion of antiphosphotyrosine precipitable receptors. After tyrosine kinase was maximally activated by iv insulin injection (in vivo), antiphosphotyrosine antibodies precipitated 60% and 38% of insulin receptors from muscle and liver, respectively. Addition of insulin in vitro to in vivo activated receptors increased the proportion of antiphosphotyrosine antibody-precipitable receptors in both tissues but increased the tyrosine kinase activity only in liver-derived receptors, indicating that most activatable insulin receptors reside on the plasmalemma in muscle whereas a significant proportion (35%) of liver receptors are not accessible to insulin in vivo. No tissue specific differences were apparent in the interaction of three site specific anti-j8-subunit antibodies with the receptors. Conclusions: 1) The intrinsic kinase activity per insulin binding site is less in liver than in muscle. This reflects in part the greater proportion of insulin receptors from liver which do not autophosphorylate on tyrosine upon insulin binding. 2) Some insulin receptors can be phosphorylated on tyrosine in vitro without concomitant exogenous tyrosine kinase activation. (Endocrinology 122: 427–437, 1988).

Footnotes

^* Supported by Grant AM-02001 from the NIDDK and a grant from the Juvenile Diabetes Foundation International (to M.G.B.). Parts of this paper were presented at the Annual Meeting of the American Federation for Clinical Research, San Diego, CA, May 1987 [Clin Res 35:499 (Abstract)].

Supported by the Medical Scientist Training Program of the Medical University of South Carolina. Present address: Department of Medicine, University of California, San Francisco, CA 94143.

Received May 5, 1987.