G(q/11) is involved in insulin-stimulated inositol phosphoglycan putative mediator generation in rat liver membranes: co-localization of G(q/11) with the insulin receptor in membrane vesicles.
Insulin signaling to generate inositol phosphoglycans (IPGs) was demonstrated to occur via the participation of the heterotrimeric G-proteins G(q/11). IPGs were measured as two specific inositol markers, myo-inositol and chiro-inositol after strong acid hydrolysis. Insulin and Pasteurella multocida toxin (PMT) generated both myo-inositol and chiro-inositol IPGs in a dose-dependent manner. PMT has been shown to activate G(q) specifically. Insulin action was abrogated by pre-treatment with anti G(q/11) antibody. Western blotting demonstrated the enrichment of both insulin receptor beta subunit and G(q/11) in the liver membrane vesicles. Vesicles also contained clathrin, caveolin PLC beta 1 and PLC Delta. Immunogold staining revealed the co-localization of both insulin receptor beta subunit and G(q/11) in an approximate stochiometric ratio of 1:3. No vesicles were detected with either component alone. The present and considerable published data provide strong evidence for insulin signaling both via a tyrosine kinase cascade mechanism and via heterotrimeric G-protein interactions.
Sleight
S
S
Insmed, 23060, Glen Allen, VA, USA
Wilson
B A
BA
Heimark
D B
DB
Larner
J
J
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D011134:Polysaccharides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism*
D007295:Inositol Phosphates; D007328:Insulin; D011134:Polysaccharides; C028039:inositol phosphate glycan; D011972:Receptor, Insulin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins