Different effects on mitogenesis and transformation of a mutation at tyrosine 1251 of the insulin-like growth factor I receptor.
The wild type insulin-like growth factor I (IGF-I) receptor has both mitogenic and transforming activities. We have examined the effect of point mutations at tyrosine residues 1250 and 1251 on these two properties of the receptor. For this purpose, we stably transfected plasmids expressing mutant and wild type receptors into R- cells, which are 3T3-like cells, derived from mouse embryos with a targeted disruption of the IGF-I receptor genes, and therefore devoid of endogenous IGF-I receptors. A tyrosine to phenylalanine mutation of either the 1250 or 1251 residue, or both, has no effect on the ability of the receptor to transmit a mitogenic signal. However, the tyrosine 1251 mutant receptor and the double mutant have lost the ability to transform R- cells (colony formation in soft agar), even when the receptors are expressed at very high levels, while the Y1250F mutant is fully transforming. These experiments show that the 1251 tyrosine residue is required for the transforming activity of the IGF-I receptor.
Miura
M
M
Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Surmacz
E
E
Burgaud
J L
JL
Baserga
R
R
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers / Q000737:chemistry; D005799:Genes, Dominant; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017354:Point Mutation; D011506:Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry; D017526:Receptor, IGF Type 1 / Q000737:chemistry*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine / Q000737:chemistry
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D017931:DNA Primers; D011506:Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1