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  • Title: Knock-down of LAR protein tyrosine phosphatase induces insulin resistance.
    Author: Mander A, Hodgkinson CP, Sale GJ.
    Journal: FEBS Lett; 2005 Jun 06; 579(14):3024-8. PubMed ID: 15896785.
    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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