Mutational analysis of the mitogenic and transforming activities of the insulin-like growth factor I receptor.

THe type 1 insulin-like growth factor receptor (IGF-IR) plays an important role in mitogenesis and transformation. It has been previously shown that mitogenic signaling and transforming activity of the IGF-IR can be dissociated: a receptor truncated at residue 1229 (C-terminus) is fully mitogenic, in terms of its response to IGF-I, but cannot transform 3T3-like cells that are devoid of endogenous IGF-IRs (R- cells). We have extended our mutational analysis of the C-terminus of the human IGF-IR, by stably transfecting several mutant receptors into R- cells, and testing the resulting cell lines for IGF-I-mediated mitogenic response and formation of colonies in soft agar. The results indicate that the transforming domain of the IGF-IR can be localized between residues 1245 and 1310, these sequences being not required for mitogenic signaling. Within these residues, there are at least two areas that contribute to the transforming activity of the receptor.