PMID: 8603747Feb 12, 1996Paper

Diacylglycerol directly stimulates the insulin receptor tyrosine kinase

FEBS Letters
R S Arnold, A C Newton

Abstract

Studies with detergent:lipid mixed micelles reveal that diacylglycerol directly stimulates the intrinsic tyrosine kinase activity of the insulin receptor. Kinetic analyses indicate that diacylglycerol activates the kinase by causing a marked increase in the affinity of the receptor for insulin. In contrast, diacylglycerol has no effect on the insulin receptor's catalytic activity or its affinity for ATP. Stimulation of the insulin receptor is not a result of protein kinase C activation. First, phorbol myristate acetate, a potent activator of protein kinase C, has no effect on insulin receptor activity. Second, the activation by diacylglycerol is not stereospecific, in marked contrast to the specificity for 1,2-diacyl-sn-glycerol in the activation of protein kinase C. Because circulating levels of insulin are below the Kd of the insulin receptor for insulin, the ability of diacylglycerol to modulate the affinity of the receptor for ligand suggests that increases in cellular levels of diacylglycerol directly sensitize the receptor to insulin.

References

Aug 6, 1991·Biochemistry·R S Arnold, A C Newton
Dec 16, 1991·Biochemical and Biophysical Research Communications·M KellererH U Häring
Jan 12, 1990·European Journal of Biochemistry·G Grunberger, J Levy
Sep 18, 1987·Science·O M Rosen
Nov 15, 1988·The Biochemical Journal·R V FareseR J Pollet
Dec 15, 1987·The Biochemical Journal·R M KramerD Deykin
Jan 1, 1974·Annual Review of Biochemistry·P Cuatrecasas
Nov 30, 1983·Biochemical and Biophysical Research Communications·R M DawsonR F Irvine
Oct 30, 1984·Biochemical and Biophysical Research Communications·S Das, R P Rand
Dec 1, 1995·The Journal of Biological Chemistry·A C Newton

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Citations

Nov 8, 2001·American Journal of Physiology. Cell Physiology·T AndohT Higashi
May 7, 2002·Life Sciences·Chien-Yun HsiangTin-Yun Ho
Sep 12, 1998·Biochimica Et Biophysica Acta·A M Jiménez-MonrealJ C Gómez-Fernández
Mar 7, 2002·Critical Reviews in Oncology/hematology·Janine G EinspahrDavid S Alberts
Jun 15, 2007·Chemistry and Physics of Lipids·Juan C Gómez-Fernández, Senena Corbalán-García
Feb 4, 1999·Biophysical Journal·V MicolJ C Gómez-Fernández

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