SciELO - Scientific Electronic Library Online

 
vol.31 issue11Association of hepatic nuclear factor-4 in the apolipoprotein B promoter: a preliminary reportInsulin receptor has tyrosine kinase activity toward Shc in rat liver author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Brazilian Journal of Medical and Biological Research

On-line version ISSN 1414-431X

Abstract

LIMA, M.H.M.; ZAMBELLI, J.E.; CARVALHO, C.R.O.  and  SAAD, M.J.A.. The insulin receptor substrate 1 associates with phosphotyrosine phosphatase SHPTP2 in liver and muscle of rats. Braz J Med Biol Res [online]. 1998, vol.31, n.11, pp. 1409-1413. ISSN 1414-431X.  http://dx.doi.org/10.1590/S0100-879X1998001100007.

Insulin stimulates the tyrosine kinase activity of its receptor resulting in the phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1) which, in turn, associates with proteins containing SH2 domains. It has been shown that IRS-1 associates with the tyrosine phosphatase SHPTP2 in cell cultures. While the effect of the IRS-1/SHPTP2 association on insulin signal transduction is not completely known, this association may dephosphorylate IRS-1 and may play a critical role in the mitogenic actions of insulin. However, there is no physiological demonstration of this pathway of insulin action in animal tissues. In the present study we investigated the ability of insulin to induce association between IRS-1 and SHPTP2 in liver and muscle of intact rats, by co-immunoprecipitation with anti-IRS-1 antibody and anti-SHPTP2 antibody. In both tissues there was an increase in IRS-1 association with SHPTP2 after insulin stimulation. This association occurred when IRS-1 had the highest level of tyrosine phosphorylation and the decrease in this association was more rapid than the decrease in IRS-1 phosphorylation levels. The data provide evidence against the participation of SHPTP2 in IRS-1 dephosphorylation in rat tissues, and suggest that the insulin signal transduction pathway in rat tissues is related mainly to the mitogenic effects of the hormone.

Keywords : insulin action; insulin receptor substrate; phosphotyrosine phosphatase; SHPTP2.

        · text in English     · pdf in English