Biochemistry, Biophysics, and Structural Biology Commons^™

Ahsg-Fetuin Blocks The Metabolic Arm Of Insulin Action Through Its Interaction With The 95-Kd Beta-Subunit Of The Insulin Receptor, Anton Scott Goustin

Anton Scott Goustin

We previously have shown that Ahsg, a liver glycoprotein, inhibits insulin receptor (InsR) tyrosine kinase (TK) activity and the ERK1/2 mitogenic signaling arm of insulin signaling. Here we show that Ahsg blocks insulin-stimulated GLUT4 translocation and Akt activation in intact cells (mouse myoblasts). Furthermore, Ahsg inhibits InsR autophosphorylation of highly-purified insulin holoreceptors in a cell-free, ATP-dependent system,with an IC50within the range of single-chain Ahsg concentrations in human serum. Binding of 125I-insulin to living cells overexpressing the InsR shows a dissociation constant (KD) of 250 pM, unaltered in the presence of 300 nMAhsg. Amutant InsR cDNA encoding the signal peptide, the …