Association of the insulin receptor with phospholipase C-gamma (PLCgamma) in 3T3-L1 adipocytes suggests a role for PLCgamma in metabolic signaling by insulin

Details

Serval ID
serval:BIB_341C603A4ADE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Association of the insulin receptor with phospholipase C-gamma (PLCgamma) in 3T3-L1 adipocytes suggests a role for PLCgamma in metabolic signaling by insulin
Journal
Journal of Biological Chemistry
Author(s)
Kayali  A. G., Eichhorn  J., Haruta  T., Morris  A. J., Nelson  J. G., Vollenweider  P., Olefsky  J. M., Webster  N. J.
ISSN
0021-9258 (Print)
Publication state
Published
Issued date
05/1998
Volume
273
Number
22
Pages
13808-18
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S. --- Old month value: May 29
Abstract
Phospholipase C-gamma (PLCgamma) is the isozyme of PLC phosphorylated by multiple tyrosine kinases including epidermal growth factor, platelet-derived growth factor, nerve growth factor receptors, and nonreceptor tyrosine kinases. In this paper, we present evidence for the association of the insulin receptor (IR) with PLCgamma. Precipitation of the IR with glutathione S-transferase fusion proteins derived from PLCgamma and coimmunoprecipitation of the IR and PLCgamma were observed in 3T3-L1 adipocytes. To determine the functional significance of the interaction of PLCgamma and the IR, we used a specific inhibitor of PLC, U73122, or microinjection of SH2 domain glutathione S-transferase fusion proteins derived from PLCgamma to block insulin-stimulated GLUT4 translocation. We demonstrate inhibition of 2-deoxyglucose uptake in isolated primary rat adipocytes and 3T3-L1 adipocytes pretreated with U73122. Antilipolytic effect of insulin in 3T3-L1 adipocytes is unaffected by U73122. U73122 selectively inhibits mitogen-activated protein kinase, leaving the Akt and p70 S6 kinase pathways unperturbed. We conclude that PLCgamma is an active participant in metabolic and perhaps mitogenic signaling by the insulin receptor in 3T3-L1 adipocytes.
Keywords
3T3 Cells Adipocytes/enzymology/*metabolism Animals Deoxyglucose/metabolism Enzyme Inhibitors/pharmacology Estrenes/pharmacology Glucose Transporter Type 4 Insulin/*metabolism Isoenzymes/antagonists & inhibitors/*metabolism Lipolysis Male Mice Microinjections Monosaccharide Transport Proteins/metabolism *Muscle Proteins Phospholipase C/antagonists & inhibitors/*metabolism Phospholipase C gamma Pyrrolidinones/pharmacology Rats Rats, Sprague-Dawley Receptor, Insulin/*metabolism Recombinant Fusion Proteins/metabolism *Signal Transduction src Homology Domains
Pubmed
Web of science
Create date
25/01/2008 14:06
Last modification date
20/08/2019 13:20
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