Insight into the association between phospholipase C-γ1 and the insulin receptor

Authors

  • Hyeung-Jin Jang
  • Yong-Kook Kwon
  • Sutapa Kole
  • Michel Bernier

Abstract

An intense investigation is underway to identify the signaling intermediates that interact directly with the insulin receptor (IR) as they appear to be associated with the transmission of insulin action.We recently reported the inducible association of phospholipase C (PLC)γ1 with the IR and its involvement in the transduction of insulin-mediated signals through activation of the Ras/extracellular-regulated kinase pathway. Akin to protein phosphorylation, redox regulation represents an important metabolic modulator of cellular functions. In this study, various mutant forms of PCLγ1 were generated to identify putative key redox-sensitive cysteines that provide sites for a number of post-translational modifications. Toward this aim, two methods were used that demonstrate the presence of oxidation-sensitive cysteine residues in PCLγ1. Using site-directed mutagenesis experiments we found that two cysteines in PCLγ1 (Cys-8 and Cys-12) were modified with hydrogen peroxide and protected against a host of reactive oxygen species through pharmacological inhibition of cellular membrane oxidases. The data suggest that the amino-terminal region of PCLγ1 contains reactive cysteine-SH groups that are exquisitely sensitive to redox regulation and which are associated with efficient interaction with the IR. The importance of these findings is already asserting themselves in studies reporting the regulatory role of cellular redox in insulin signal transduction.

Published

2007-12-28