title: Possible direct linkage of insulin-like growth factor-II receptor with guanine nucleotide-binding proteins.
abstract: In mouse Balb/c3T3 fibroblasts, insulin-like growth factor (IGF)-II activates a calcium-permeable cation channel through a cell surface IGF-II receptor (Kojima, I., Nishimoto, I., Iiri, T., Ogata, E., and Rosenfeld, R. G. (1988) Biochem. Biophys. Res. Commun. 154, 9-19; Matsunaga, H., Nishimoto, I., Kojima, I., Yamashita, N., Kurokawa, K., and Ogata, E. (1988) Am. J. Physiol. 255, C442-C446). In the action of IGF-II, a pertussis toxin (or islet-activating protein; IAP)-sensitive GTP-binding protein (G protein) is inferred to be involved (Nishimoto, I., Hata, Y., Ogata, E., and Kojima, I. (1987) J. Biol. Chem. 262, 12120-12126). In the present study, we examined the direct coupling of the IGF-II receptor with G proteins. In broken Balb/c3T3 cell membranes, 10 nM IGF-II rapidly attenuated the IAP-catalyzed ADP-ribosylation of a 40-kDa protein in a manner requiring magnesium ion. The IGF-II-mediated attenuation in the IAP substrate activity was 80% recovered after washing off IGF-II and inhibited by coexisting guanosine 5'-O-(2-thiodiphosphate), while either aluminum fluoride solution (10 mM NaF plus 100 microM AlCl3) or 100 microM guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) reproduced the action of IGF-II. When purified IAP substrate G proteins (Gi1, Gi2, G0) were incubated with IGF-II in the presence of membranes from IAP-treated Balb/c3T3 cells, the attenuation in the IAP substrate activity was evident in Gi2, but not in Gi1 or G0. On the other hand, 10 nM insulin had no effect on the modification of the 40-kDa IAP substrate in Balb/c3T3 cell membranes, whereas 10 nM IGF-I elicited a slow onset of the IAP sensitivity attenuation from the 40-kDa protein. However, the specific involvement of the IGF-II receptor in the modification of the IAP substrate induced by low concentrations of IGF-II was suggested by the observations that (i) IGF-I receptor-lacking cell membranes were effective for the Gi2 modification by IGF-II, (ii) the ability of membranes to mediate the action of IGF-II was markedly attenuated in IGF-II receptor-lacking cell membranes, and (iii) agonistic anti-IGF-II receptor antibody mimicked the action of IGF-II on the 40-kDa protein in Balb/c3T3 cell membranes in a dose-dependent manner similar to that observed in the antibody-induced blocking of membrane IGF-II binding.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Nishimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Murayama
authors.forename: T
authors.initials: T
authors.lastname: Katada
authors.forename: M
authors.initials: M
authors.lastname: Ui
authors.forename: E
authors.initials: E
authors.lastname: Ogata
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002999:Clone Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism* / Q000494:pharmacology; D007624:KB Cells / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D037342:Pertussis Toxin; D051381:Rats; D011956:Receptors, Cell Surface / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000378:metabolism
chemical_list: D007106:Immune Sera; D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins