GIPC participates in G protein signaling downstream of insulin-like growth factor 1 receptor.
Several recent studies have demonstrated that insulin-like growth factor (IGF)-1-induced mitogen-activated protein kinase (MAP kinase) activation is abolished by pertussis toxin, suggesting that trimeric G proteins of the G(i) class are novel cellular targets of the IGF-1 signaling pathway. We report here that the intracellular domain of the Xenopus IGF-1 receptor is capable of binding to the Xenopus homolog of mammalian GIPC, a PDZ domain-containing protein previously identified as a binding partner of G(i)-specific GAP (RGS-GAIP). Binding of xGIPC to xIGF-1 receptor is independent of the kinase activity of the receptor and appears to require the PDZ domain of xGIPC. Injection of two C-terminal truncation mutants that retained the PDZ domain blocked IGF-1-induced Xenopus MAP kinase activation and oocyte maturation. While full-length xGIPC injection did not significantly alter insulin response, it greatly enhanced human RGS-GAIP in stimulating the insulin response in frog oocytes. This represents the first demonstration that GIPC x RGS-GAIP complex acts positively in IGF-1 receptor signal transduction.
Booth
Ronald A
RA
Ottawa Health Research Institute, Ottawa Hospital, Ottawa K1Y 4E9, Canada.
Cummings
Cathy
C
Tiberi
Mario
M
Liu
X Johné
XJ
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008322:Mammals; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology*; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D014982:Xenopus laevis; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C492009:GIPC1 protein, human; C115271:Gipc1 protein, mouse; C492008:Gipc1 protein, rat; D009479:Neuropeptides; D017526:Receptor, IGF Type 1; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins