Document Detail


Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signaling.
MedLine Citation:
PMID:  21707536     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin receptor (IR) activation and glucose homeostasis, but the precise molecular mechanisms governing PTP1B substrate selectivity and the regulation of insulin signaling remain unclear. Here we have taken advantage of Drosophila as a model organism to establish the role of the SH3/SH2 adaptor protein Dreadlocks (Dock) 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 signaling by recruiting PTP61F/PTP1B to its substrate the IR.
Authors:
Chia-Lun Wu; Bree Buszard; Chun-Hung Teng; Wei-Lin Chen; Coral Warr; Tony Tiganis; Tzu-Ching Meng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-27
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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