Association of Heterotrimeric Gi with the Insulin-like Growth Factor-I Receptor
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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| Published in: | The Journal of biological chemistry 2000-01, Vol.275 (4), p.2255-2258 |
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| Main Authors: | , , , , |
| Format: | Article |
| Language: | eng |
| Online Access: | Get full text |
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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 Gi class of GTP-binding proteins, inhibits IGF-I-mediated activation of MAPK, and a specific role for Gβγ subunits in IGF-I signaling was shown. In the present study, we have investigated the role of heterotrimeric Gi 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. Gαi and Gβ subunits were associated with IGF-IR immunoprecipitates. Similarly, in IGF-IR-null mouse embryo fibroblasts transfected with the human IGF-IR, Gi was complexed with the IGF-IR. Gαs was not associated with the IGF-IR in any cell type. IGF-I induced the release of the Gβ subunits from the IGF-IR but had no effect on the association of Gαi. These results demonstrate an association of heterotrimeric Gi with the IGF-IR and identify a discrete pool of Gβγ subunits available for downstream signaling following stimulation with IGF-I. |
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| ISSN: | 0021-9258 1083-351X |