Knock-down of LAR protein tyrosine phosphatase induces insulin resistance.

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.

• Authors: Ann Mander, Conrad P Hodgkinson, Graham J Sale
• Journal: FEBS letters (FEBS Lett) Vol. 579 Issue 14 Pg. 3024-8 (Jun 06 2005) ISSN: 0014-5793 [Print] England
• PMID: 15896785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• RNA, Small Interfering
• Receptors, Cell Surface
• Phosphotyrosine
• Receptor, Insulin
• PTPRA protein, human
• Protein Tyrosine Phosphatases
• Receptor-Like Protein Tyrosine Phosphatases, Class 4

Topics

• Cell Line
• Humans
• Insulin (pharmacology)
• Insulin Resistance (genetics)
• Phosphotyrosine (metabolism)
• Protein Tyrosine Phosphatases (deficiency, genetics, metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Receptor, Insulin (metabolism)
• Receptor-Like Protein Tyrosine Phosphatases, Class 4
• Receptors, Cell Surface (deficiency, genetics, metabolism)
• Signal Transduction (drug effects)
• Substrate Specificity