Cellular growth inhibition by TGF-beta1 involves IRS proteins.
In Mv1Lu cells, insulin partially reverses transforming growth factor-beta1 (TGF-beta1) growth inhibition in the presence of alpha5beta1 integrin antagonists. TGF-beta1 appears to induce phosphorylation of IRS-2 in these cells; this is inhibited by a TGF-beta antagonist known to reverse TGF-beta growth inhibition. Stable transfection of 32D myeloid cells (which lack endogenous IRS proteins and are insensitive to growth inhibition by TGF-beta1) with IRS-1 or IRS-2 cDNA confers sensitivity to growth inhibition by TGF-beta1; this IRS-mediated growth inhibition can be partially reversed by insulin in 32D cells stably expressing IRS-2 and the insulin receptor (IR). These results suggest that growth inhibition by TGF-beta1 involves IRS proteins.
Huang
Shuan Shian
SS
Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA. huangss@slu.edu
Leal
Sandra M
SM
Chen
Chun-Lin
CL
Liu
I-Hua
IH
Huang
Jung San
JS
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009052:Leukemia Virus, Murine; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D018076:DNA, Complementary; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D039081:Integrin alpha5beta1; D047908:Intracellular Signaling Peptides and Proteins; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004247:DNA; D011972:Receptor, Insulin