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Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling


Wu, C-L and Buszard, B and Teng, C-H and Chen, W-L and Warr, CG and Tiganis, T and Meng, T-C, Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling, Biochemical Journal, 439, (1) pp. 151-159. ISSN 0264-6021 (2011) [Refereed Article]

DOI: doi:10.1042/BJ20110799


PTP1B (protein tyrosine phosphatase 1B) is a negative regulator of IR (insulin receptor) activation and glucose homoeostasis, but the precise molecular mechanisms governing PTP1B substrate selectivity and the regulation of insulin signalling remain unclear. In the present study we have taken advantage of Drosophila as a model organism to establish the role of the SH3 (Src homology 3)/SH2 adaptor protein Dock (Dreadlocks) and its mammalian counterpart Nck in IR regulation by PTPs. We demonstrate that the PTP1B orthologue PTP61F dephosphorylates the Drosophila IR in S2 cells in vitro and attenuates IR-induced eye overgrowth in vivo. Our studies indicate that Dock forms a stable complex with PTP61F and that Dock/PTP61F associate with the IR in response to insulin. We report that Dock is required for effective IR dephosphorylation and inactivation by PTP61F in vitro and in vivo. Furthermore, we demonstrate that Nck interacts with PTP1B and that the Nck/PTP1B complex inducibly associates with the IR for the attenuation of IR activation in mammalian cells. Our studies reveal for the first time that the adaptor protein Dock/Nck attenuates insulin signalling by recruiting PTP61F/PTP1B to its substrate, the IR.

Item Details

Item Type:Refereed Article
Keywords:Dock/Nck; Drosophila; Insulin receptor; Insulin signalling; Protein tyrosine phosphatase 61F/protein tyrosine phosphatase 1B (PTP61F/PTP1B); Tyrosine phosphorylation; adaptor protein; docking protein; insulin receptor; Nck protein; protein SH3
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Signal transduction
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Warr, CG (Professor Coral Warr)
ID Code:131877
Year Published:2011
Web of Science® Times Cited:23
Deposited By:Office of the School of Medicine
Deposited On:2019-04-10
Last Modified:2019-04-10

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