Effect of mutations at serines 1280-1283 on the mitogenic and transforming activities of the insulin-like growth factor I receptor.
The insulin-like growth factor I receptor (IGF-IR) controls the extent of cell proliferation in a variety of cell types by at least 3 different ways: it is mitogenic, it causes transformation, and it protects cells from apoptosis. Previous reports indicated that certain domains in the C terminus of the IGF-IR transmitted a transforming signal that is additional to and separate from the mitogenic signal. We have now mutated the four serine residues at 1280-1283 of the IGF-IR, and transfected the mutant receptor into R- cells. Cells expressing the mutant receptor are fully responsive to IGF-I mediated mitogenesis, but are not transformed (no colony formation in soft agar). Several downstream signal transducers are not affected by the mutation, again suggesting a separate pathway for transformation. The mutant receptor can act as a dominant negative for growth, but cannot induce apoptosis in cells with endogenous wild-type receptors.
Li
S
S
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Resnicoff
M
M
Baserga
R
R
D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D017931:DNA Primers; D051379:Mice; D008934:Mitogens / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics*; D015398:Signal Transduction; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D017931:DNA Primers; D008934:Mitogens; D014443:Tyrosine; D012694:Serine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017526:Receptor, IGF Type 1