IRS-1 - ESSENTIAL FOR INSULIN-STIMULATED AND IL-4-STIMULATED MITOGENESIS IN HEMATOPOIETIC-CELLS

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.