IRS-1: essential for insulin- 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.
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
L M
LM
Wang
M G
MG
Myers
X J
XJ
Sun
S A
SA
Aaronson
M
M
White
J H
JH
Pierce
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D015847:Interleukin-4 / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D014443:Tyrosine; D011972:Receptor, Insulin