Association and phosphorylation-dependent dissociation of proteins in the insulin receptor complex.
Receptor tyrosine kinases have been found to interact with a variety of specific signaling molecules. To detect molecules that interact with the insulin receptor, we have produced a modified insulin receptor with an additional epitope allowing rapid purification under mild conditions of the insulin receptor complex. By this method we have found multiple proteins (including the p85 subunit of phosphatidylinositol 3'-kinase and the ras GTPase-activating protein) that specifically associate with the activated (phosphorylated) insulin receptor (insulin receptor complex proteins) but are released from the complex after they are phosphorylated on tyrosine residues. We have also shown that tyrosine phosphorylation of p85 by the activated insulin receptor blocks binding to the activated receptor. These results suggest that association of proteins with the insulin receptor complex is controlled by phosphorylation of the receptor, while dissociation of insulin receptor complex proteins is controlled in turn by phosphorylation of the proteins in the insulin receptor complex. This process results in the dispersion of phosphorylated insulin receptor complex proteins into the cell.
Zhang
W
W
Hormone Research Institute, University of California, San Francisco 94143-0534.
Johnson
J D
JD
Rutter
W J
WJ
D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D020690:GTPase-Activating Proteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D019000:Phosphotyrosine; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D017931:DNA Primers; D020690:GTPase-Activating Proteins; D046911:Macromolecular Substances; D011506:Proteins; D011993:Recombinant Fusion Proteins; D020703:ras GTPase-Activating Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011972:Receptor, Insulin