Serum alpha 2-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level.

• DOI: 10.1210/mend.7.11.7906861
• Publication Date: 2014-01-08T17:28:06Z
• Authors: P R Srinivas; A S Wagner; L V Reddy; D D Deutsch; M A Leon; A S Goustin; G Grunberger
• Keywords: IRS2; Insulin receptor substrate; GRB10; IRS1

The insulin-dependent tyrosine kinase activity (TKA) of the insulin receptor (IR) plays an essential role in signaling. Thus, dysregulation IR-TKA might be important element states resistance. A phosphorylated rat hepatic glycoprotein (pp63) acting as inhibitor IR-TK has been described. In search human homolog pp63, we isolated a cDNA clone from liver lambda gt11 library. DNA sequence analysis reveals identity with mRNA product gene AHSG encoding serum protein, alpha 2-Heremans Scmid-glycoprotein (alpha 2HSG), heretofore unknown physiological function. Northern blot demonstrates 1.8-kilobase and HepG2 hepatoma cells. 2HSG, purified serum, specifically inhibits insulin-stimulated IR autophosphorylation vitro vivo well exogenous substrate phosphorylation. 2HSG also both insulin-induced phosphorylation IRS-1 association p85 subunit phosphatidylinositol-3 H-35 mitogenesis, but does not affect induction metabolic enzyme aminotransferase. compete for binding to IR. Finally, action is specific toward IR-TK; its effect extend insulin-like growth factor-I-stimulated TKA. Our results allow us assign biochemical function namely regulation at level.