IRS-1: Essential for Insulin- and IL-4-Stimulated Mitogenesis in Hematopoietic Cells

• Published in: Science (American Association for the Advancement of Science) 1993-09, Vol.261 (5128), p.1591-1594
• Main Authors: Wang, Ling-Mei, Myers, Martin G., Sun, Xiao-Jian, Aaronson, Stuart A., White, Morris, Pierce, Jacalyn H.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; Cell growth; Cell Line; Cell lines; Cell physiology; Cellular immunity; Cellular receptors; Complementary DNA; Fundamental and applied biological sciences. Psychology; Genetic vectors; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic system; Insulin; Insulin - pharmacology; Insulin Receptor Substrate Proteins; Insulin receptors; Interleukin-4 - pharmacology; Mice; Mitogens; Molecular and cellular biology; Phosphoproteins - metabolism; Phosphorylation; Receptor, Insulin - metabolism; Receptors; Receptors, Interleukin-4; Receptors, Mitogen - metabolism; Signal transduction; Transfection; Tyrosine - metabolism
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8372354

Although several interleukin-3 (IL-3)-dependent cell lines proliferate in response to IL-4 or insulin, the 32D line does not. Insulin and IL-4 sensitivity was restored to 32D cells by expression of IRS-1, the principal substrate of the insulin receptor. Although 32D cells possessed receptors for both factors, they lacked the IRS-1-related protein, 4PS, which becomes phosphorylated by tyrosine in insulin- or IL-4-responsive lines after stimulation. These results indicate that factors that bind unrelated receptors can use similar mitogenic signaling pathways in hematopoietic cells and that 4PS and IRS-1 are functionally similar proteins that are essential for insulin- and IL-4-induced proliferation.