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Tyrosine phosphorylation of R3 subtype receptor-type protein tyrosine phosphatases and their complex formations with

Yoji Murata1, Munemasa Mori, Takenori Kotani

  • 1Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|April 20, 2010
PubMed

Insights

Tyrosine phosphorylation of R3 subtype receptor-type protein tyrosine phosphatases (RPTPs) enhances their binding to Grb2 or Fyn. This modification is crucial for regulating cell morphology and lamellipodium formation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Post-translational modification regulates protein tyrosine phosphatase (PTP) function.
  • Receptor-type PTPs (RPTPs), including SAP-1, PTPRO, and VE-PTP, are key signaling molecules.
  • The R3 subtype of RPTPs has been implicated in various cellular processes.

Purpose of the Study:

  • To investigate the role of tyrosine phosphorylation in the function of R3 subtype RPTPs.
  • To explore the interaction of SAP-1, PTPRO, and VE-PTP with downstream signaling molecules.
  • To understand the contribution of tyrosine phosphorylation to RPTP-mediated cell morphology changes.

Main Methods:

  • Treatment with a PTP inhibitor to induce tyrosine phosphorylation.
  • Analysis of protein complex formation using techniques like co-immunoprecipitation.
  • Assessment of cell morphology changes, including cell spreading and lamellipodium formation, via microscopy.

Main Results:

  • Tyrosine phosphorylation was observed in the carboxyl (COOH)-terminal regions of SAP-1, PTPRO, and VE-PTP.
  • Src family kinases were identified as mediators of SAP-1 tyrosine phosphorylation.
  • Tyrosine-phosphorylated SAP-1, PTPRO, and VE-PTP formed complexes with Grb2 and Fyn.
  • Forced expression of wild-type RPTPs promoted cell spreading and lamellipodium formation, an effect diminished in non-phosphorylated forms.

Conclusions:

  • Tyrosine phosphorylation of R3 subtype RPTPs is a critical regulatory mechanism.
  • Phosphorylation enhances the formation of complexes between RPTPs and signaling adaptors like Grb2 and Fyn.
  • This process plays a significant role in modulating cell morphology and cytoskeletal dynamics.

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