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Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling

journal contribution
posted on 2023-05-20, 02:41 authored by Wu, C-L, Buszard, B, Teng, C-H, Chen, W-L, Coral WarrCoral Warr, Tiganis, T, Meng, T-C
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.

History

Publication title

Biochemical Journal

Volume

439

Pagination

151-159

ISSN

0264-6021

Department/School

Tasmanian School of Medicine

Publisher

Portland Press

Place of publication

59 Portland Place, London, England, W1N 3Aj

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the biological sciences