Effect of a mutation at tyrosine 950 of the insulin-like growth factor I receptor on the growth and transformation of cells.
Recent evidence has shown that the insulin-like growth factor I (IGF-I) receptor plays a major role in the establishment and maintenance of transformation. To identify domains in the IGF-I receptor that are necessary for transformation, the tyrosine at residue 950 of the human IGF-I receptor cDNA was mutated to phenylalanine, and the plasmid expressing the mutant receptor was stably transfected into R- cells, which are mouse embryo fibroblasts with a targeted disruption of the type 1 receptor for the insulin-like growth factors. At variance with the wild-type receptor, the Y950 mutant receptor has lost its ability to transmit an IGF-I-mediated mitogenic signal or to transform R- cells. These experiments show, for the first time, that tyrosine 950 of the IGF-I receptor is necessary for its mitogenic and transforming activities.
Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D004247:DNA / Q000096:biosynthesis; D017931:DNA Primers; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010649:Phenylalanine; D017354:Point Mutation; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine
D017931:DNA Primers; D011994:Recombinant Proteins; D014443:Tyrosine; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; D004247:DNA; D017526:Receptor, IGF Type 1