Knock-down of LAR protein tyrosine phosphatase induces insulin resistance

Mander, Ann, Hodgkinson, Conrad P. and Sale, Graham J. (2005) Knock-down of LAR protein tyrosine phosphatase induces insulin resistance. FEBS Letters, 579 (14), 3024-3028. (doi:10.1016/j.febslet.2005.04.057).

Abstract

To test the role of the leukocyte common antigen-related protein tyrosine phosphatase (LAR) as a regulator of insulin receptor (IR) signalling, an siRNA probe against LAR was developed. Knock-down of LAR induced post-receptor insulin resistance with the insulin-induced activation of PKB/Akt and MAP kinases markedly inhibited. The phosphorylation and dephosphorylation of the IR and insulin receptor substrate (IRS) proteins were unaffected by LAR knock-down. These results identify LAR as a crucial regulator of the sensitivity of two key insulin signalling pathways to insulin. Moreover, the siRNA probe provides a molecular tool of general applicability for further dissecting the precise targets and roles of LAR.

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