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Knock-down of LAR protein tyrosine phosphatase induces insulin resistance

Knock-down of LAR protein tyrosine phosphatase induces insulin resistance
Knock-down of LAR protein tyrosine phosphatase induces insulin resistance
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.
insulin receptor, protein tyrosine phosphatase, LAR, protein kinase B, MAP kinase, insulin resistance
0014-5793
3024-3028
Mander, Ann
2fcb3a33-6bb8-4463-8b06-79cd508e9d80
Hodgkinson, Conrad P.
292cc7c3-b378-4911-8353-9a8c08a1c737
Sale, Graham J.
81048025-7d8f-4218-969a-bf95ebf50b51
Mander, Ann
2fcb3a33-6bb8-4463-8b06-79cd508e9d80
Hodgkinson, Conrad P.
292cc7c3-b378-4911-8353-9a8c08a1c737
Sale, Graham J.
81048025-7d8f-4218-969a-bf95ebf50b51

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).

Record type: Article

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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More information

Submitted date: 25 March 2005
Published date: 6 June 2005
Keywords: insulin receptor, protein tyrosine phosphatase, LAR, protein kinase B, MAP kinase, insulin resistance

Identifiers

Local EPrints ID: 56336
URI: https://eprints.soton.ac.uk/id/eprint/56336
ISSN: 0014-5793
PURE UUID: afa5a390-e5ef-4ade-8fc9-75f6d0dc98f5

Catalogue record

Date deposited: 07 Aug 2008
Last modified: 13 Mar 2019 20:35

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