The role of mGrb10alpha 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, mGrb10alpha, in cell proliferation. For this purpose, a plasmid expressing mGrb10alpha was stably transfected into p6 cells and other mouse embryo fibroblast cell lines. An overexpressed mGrb10alpha inhibits IGF-I-mediated growth, causes a delay in the S and G2 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.
Morrione
A
A
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Valentinis
B
B
Resnicoff
M
M
Xu
S q
Sq
Baserga
R
R
D016475:3T3 Cells; D000818:Animals; D066246:ErbB Receptors / Q000502:physiology*; D016195:G2 Phase; D051383:GRB10 Adaptor Protein; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000502:physiology*; D017451:Receptors, Somatomedin / Q000378:metabolism; D016196:S Phase; D015398:Signal Transduction
C495959:Grb10 protein, mouse; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D017451:Receptors, Somatomedin; D051383:GRB10 Adaptor Protein; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors