Association of heterotrimeric G(i) with the insulin-like growth factor-I receptor. Release of G(betagamma) subunits upon receptor activation

The insulin-like growth factor-I receptor (IGF-IR) is a key regulator of cell proliferation and survival. Activation of the IGF-IR induces tyrosine autophosphorylation and the binding of a series of adaptor molecules, thereby leading to the activation of MAPK. It has been demonstrated that pertussis...

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Bibliographic Details
Published in:	The Journal of biological chemistry 2000-01, Vol.275 (4), p.2255-2258
Main Authors:	Hallak, H, Seiler, A E, Green, J S, Ross, B N, Rubin, R
Format:	Article
Language:	eng
Subjects:	3T3 Cells Animals Enzyme Activation GTP-Binding Protein alpha Subunits, Gi-Go - metabolism Humans Mice Mice, Inbred BALB C Mice, Knockout Mitogen-Activated Protein Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinases - metabolism Pertussis Toxin Rats Receptors, Somatomedin - genetics Receptors, Somatomedin - metabolism Signal Transduction Virulence Factors, Bordetella - pharmacology
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Summary:	The insulin-like growth factor-I receptor (IGF-IR) is a key regulator of cell proliferation and survival. Activation of the IGF-IR induces tyrosine autophosphorylation and the binding of a series of adaptor molecules, thereby leading to the activation of MAPK. It has been demonstrated that pertussis toxin, which inactivates the G(i) class of GTP-binding proteins, inhibits IGF-I-mediated activation of MAPK, and a specific role for G(betagamma) subunits in IGF-I signaling was shown. In the present study, we have investigated the role of heterotrimeric G(i) in IGF-IR signaling in neuronal cells. Pertussis toxin inhibited IGF-I-induced activation of MAPK in rat cerebellar granule neurons and NG-108 neuronal cells. G(alphai) and G(beta) subunits were associated with IGF-IR immunoprecipitates. Similarly, in IGF-IR-null mouse embryo fibroblasts transfected with the human IGF-IR, G(i) was complexed with the IGF-IR. G(alphas) was not associated with the IGF-IR in any cell type. IGF-I induced the release of the G(beta) subunits from the IGF-IR but had no effect on the association of G(alphai). These results demonstrate an association of heterotrimeric G(i) with the IGF-IR and identify a discrete pool of G(betagamma) subunits available for downstream signaling following stimulation with IGF-I.
ISSN:	0021-9258 1083-351X