Characterization of insulin receptor substrate 3 in rat liver derived cells.
In rat liver derived HTC cells transfected with and expressing human insulin receptors, there are multiple p60-70 proteins that are tyrosine phosphorylated following insulin treatment of cells. Employing antibodies to insulin receptor substrate 3 (alpha-IRS-3), we found that IRS-3 is a major p60 phosphoprotein that is tyrosine phosphorylated following insulin treatment of cells and interacts with phosphatidylinositol-3-kinase (PI3K). Majority of IRS-3 when phosphorylated appears to interact with PI3K. Tyrosine phosphorylation of IRS-3 is robust at 2 min and steadily increases up to 30-90 min of insulin treatment. Following insulin treatment of cells, some high molecular weight phosphoproteins are coimmunoprecipitated with alpha-IRS-3. In summary, IRS-3 is the major p60 protein that is tyrosine phosphorylated and interacts with PI3K in HTC rat liver derived cells following insulin treatment of cells. Unlike related IRS-1/2 that is transiently phosphorylated, IRS-3 shows robust and prolonged tyrosine phosphorylation upon insulin treatment of cells and may play a role in delayed and/or prolonged insulin actions.
Choi
W S
WS
Department of Physiology and Biophysics, University of Southern California, Los Angeles 90033, USA.
Sung
C K
CK
D000818:Animals; D002460:Cell Line; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008970:Molecular Weight; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
C491585:IRS3P protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C491584:Irs3 protein, rat; D010750:Phosphoproteins; D019000:Phosphotyrosine; D019869:Phosphatidylinositol 3-Kinases