Article: article from journal or magazin.
Insulin and insulin-like growth factor I receptors utilize different G protein signaling components.
The Journal of biological chemistry
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. - Publication Status: ppublish
We examined the role of heterotrimeric G protein signaling components in insulin and insulin-like growth factor I (IGF-I) action. In HIRcB cells and in 3T3L1 adipocytes, treatment with the Galpha(i) inhibitor (pertussis toxin) or microinjection of the Gbetagamma inhibitor (glutathione S-transferase-betaARK) inhibited IGF-I and lysophosphatidic acid-stimulated mitogenesis but had no effect on epidermal growth factor (EGF) or insulin action. In basal state, Galpha(i) and Gbeta were associated with the IGF-I receptor (IGF-IR), and after ligand stimulation the association of IGF-IR with Galpha(i) increased concomitantly with a decrease in Gbeta association. No association of Galpha(i) was found with either the insulin or EGF receptor. Microinjection of anti-beta-arrestin-1 antibody specifically inhibited IGF-I mitogenic action but had no effect on EGF or insulin action. beta-Arrestin-1 was associated with the receptors for IGF-I, insulin, and EGF in a ligand-dependent manner. We demonstrated that Galpha(i), betagamma subunits, and beta-arrestin-1 all play a critical role in IGF-I mitogenic signaling. In contrast, neither metabolic, such as GLUT4 translocation, nor mitogenic signaling by insulin is dependent on these protein components. These results suggest that insulin receptors and IGF-IRs can function as G protein-coupled receptors and engage different G protein partners for downstream signaling.
3T3 Cells, Animals, Antibodies, Arrestins, Cell Division, Cell Line, Cyclic AMP-Dependent Protein Kinases, Fibroblasts, Glutathione Transferase, Heterotrimeric GTP-Binding Proteins, Humans, Insulin, Insulin-Like Growth Factor I, Kinetics, Mice, Pertussis Toxin, Rats, Receptor, Epidermal Growth Factor, Receptor, IGF Type 1, Receptor, Insulin, Recombinant Fusion Proteins, Virulence Factors, Bordetella, beta-Adrenergic Receptor Kinases
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