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Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling

Chia-Lun Wu1, Bree Buszard, Chun-Hung Teng

  • 1Institute of Biological Chemistry, Academia Sinica, Taipei, 115 Taiwan.

The Biochemical Journal
|June 29, 2011
PubMed

Insights

The adaptor protein Dock/Nck recruits phosphatases PTP61F/PTP1B to the insulin receptor (IR), attenuating insulin signaling. This reveals a novel mechanism for regulating glucose homeostasis.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Endocrinology

Background:

  • Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin receptor (IR) activation and glucose homeostasis.
  • The precise mechanisms of PTP1B substrate selectivity and insulin signaling regulation are not fully understood.

Purpose of the Study:

  • To investigate the role of the adaptor protein Dock (Dreadlocks) and its mammalian counterpart Nck in the regulation of IR by protein tyrosine phosphatases (PTPs).

Main Methods:

  • Utilized Drosophila as a model organism to study PTP1B orthologue PTP61F and its interaction with the IR.
  • Employed in vitro and in vivo experiments to assess dephosphorylation, complex formation, and insulin signaling attenuation.

Main Results:

  • Demonstrated that PTP61F dephosphorylates the Drosophila IR and attenuates IR-induced eye overgrowth.
  • Showed that Dock forms a stable complex with PTP61F, associating with the IR upon insulin stimulation.
  • Confirmed Dock's requirement for PTP61F-mediated IR dephosphorylation and inactivation.
  • Established that Nck interacts with PTP1B, forming a complex that associates with the IR to attenuate its activation in mammalian cells.

Conclusions:

  • The adaptor proteins Dock/Nck play a crucial role in attenuating insulin signaling.
  • Dock/Nck achieve this by recruiting PTP61F/PTP1B to their substrate, the IR, revealing a novel regulatory pathway.

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