The role of mGrb10 alpha in insulin-like growth factor I-mediated growth

Several isoforms of Grb10 are known to interact with either the insulin receptor or the insulin-like growth factor I (IGF-I) receptor, or both. Inasmuch as the data in the literature on the function of Grb10 are not-always concordant, we have investigated the role of one of these isoforms, mGrb10 alpha, in cell proliferation. For this pul-pose, a plasmid expressing mGrb10 alpha was stably transfected into p6 cells and other mouse embryo fibroblast cell lines, An overexpressed mGrb10 alpha inhibits IGF-l-mediated growth, causes a delay in the S and G(2) phases of the cell cycle, and partially reverses the transformed phenotype. In contrast, it has no effect on insulin stimulation of cell proliferation These studies indicate that this isoform of Grb10 has an inhibitory effect on IGF-I signaling of cell proliferation.