The alpha beta monomer of the insulin receptor has hormone-responsive tyrosine kinase activity.
Insulin receptors from turkey erythrocyte membranes exist as monomers and dimers when membranes are solubilized with detergent. We examined the ability of monomers and dimers to act as protein kinases to effect both autophosphorylation of the receptor and phosphorylation of an exogenous substrate. After separation by sucrose-density-gradient centrifugation, only receptor dimers show significant basal and insulin-stimulated kinase activity, whereas material at the position of receptor monomers is not active. Partial reduction of the membrane-bound receptors with dithiothreitol, however, produces a receptor monomer containing an alpha and a beta chain which has protein kinase activity similar to that of the original dimers. With rat adipocyte plasma membranes, which in the absence of reducing agents only contain receptor dimers, reduction with dithiothreitol also produces monomers with receptor kinase activity. Receptor monomer hormone-dependent kinase activity is insensitive to receptor concentration and shows stimulation after immobilization on an affinity support.
Mortensen
E R
ER
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Drachman
J G
JG
Guidotti
G
G
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D004229:Dithiothreitol; D004591:Electrophoresis, Polyacrylamide Gel; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000737:chemistry / Q000378:metabolism*; D014422:Turkeys
D006728:Hormones; D007328:Insulin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D008274:Magnesium; D004229:Dithiothreitol