H. Hallak et al., Association of heterotrimeric G(i) with the insulin-like growth factor-I receptor - Release of G(beta gamma) subunits upon receptor activation, J BIOL CHEM, 275(4), 2000, pp. 2255-2258
The insulin-like growth factor-I receptor (IGF-IR) is a key regulator of ce
ll proliferation and survival. Activation of the IGF-IR induces tyrosine au
tophosphorylation 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(beta gamma) su
bunits in IGF-I signaling was shown. In the present study, we have investig
ated the role of heterotrimeric Gi in IG;F-IR signaling in neuronal cells.
Pertussis toxin inhibited IGF-I-induced activation of MAPK in rat cerebella
r granule neurons and NG-108 neuronal cells. G(alpha i) and Gp subunits wer
e associated with IGF-IR immunoprecipitates. Similarly, in IGF-IR-null mous
e embryo fibroblasts transfected with the human IG;F-IR, Gi was complexed w
ith the IGF-IR. G(alpha s) was not associated with the IGF-IR in any cell t
ype. IGF-I induced the release of the Gp subunits from the IGF-IR but had n
o effect on the association of G(alpha i). These results demonstrate an ass
ociation of heterotrimeric Gi with the IGF-IR and identify a discrete pool
of G(beta gamma) Subunits available for downstream signaling following stim
ulation with IGF-I.