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PTP-PEST targets a novel tyrosine site in p120 catenin to control epithelial cell motility and Rho GTPase activity

Rosario Espejo1, Yowjiun Jeng, Adriana Paulucci-Holthauzen

  • 1Sealy Center for Cancer Biology and UTMB Comprehensive Cancer Center, University of Texas Medical Branch, Galveston, TX 77555, USA.

Journal of Cell Science
|November 29, 2013
PubMed

Insights

The protein tyrosine phosphatase PTP-PEST directly dephosphorylates p120 catenin (p120), a key regulator of adherens junctions. This dephosphorylation controls p120

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Tyrosine phosphorylation regulates adherens junction proteins like p120 catenin (p120).
  • The precise mechanisms governing p120 phosphorylation by protein tyrosine phosphatases (PTPs) remain unclear.
  • PTP-PEST is a known regulator of cell adhesion and motility.

Purpose of the Study:

  • To elucidate the role of PTP-PEST in regulating p120 catenin phosphorylation.
  • To investigate how PTP-PEST-mediated p120 dephosphorylation impacts epithelial cell behavior.
  • To identify the specific site of PTP-PEST action on p120.

Main Methods:

  • Substrate trapping assays to identify direct PTP-PEST targets.
  • Stable shRNA knockdown of PTP-PEST in colon carcinoma cells.
  • Analysis of p120 phosphorylation, localization, and association with other proteins (E-cadherin, VAV2, cortactin).
  • Assessment of cell motility, Rac1, and RhoA GTPase activity.
  • Site-directed mutagenesis of p120.

Main Results:

  • PTP-PEST directly dephosphorylates p120 catenin at tyrosine 335.
  • PTP-PEST knockdown increases p120 tyrosine phosphorylation, reduces E-cadherin association, and enhances cell motility.
  • PTP-PEST knockdown alters Rho GTPase activity (increased Rac1, decreased RhoA) and promotes p120 localization to lamellipodia.
  • A p120 Y335F mutant phenocopies PTP-PEST knockdown effects, failing to interact with VAV2 or rescue motility.

Conclusions:

  • PTP-PEST directly dephosphorylates p120 at Tyr335, influencing its interaction with VAV2 and cortactin.
  • PTP-PEST controls epithelial cell motility by regulating p120 phosphorylation status and its downstream effects on Rho GTPases.
  • These findings reveal a novel mechanism by which PTP-PEST modulates cell adhesion and migration through p120 catenin regulation.
Keywords:
Cell motilityPTPRho GTPasep120 catenin

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