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

Rosario Espejo, Yowjiun Jeng, Adriana Paulucci-Holthauzen, William Rengifo-Cam, Krysta Honkus, Panagiotis Z Anastasiadis, Sarita K. Sastry

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Tyrosine phosphorylation is implicated in regulating the adherens junction protein, p120 catenin (p120), however, the mechanisms are not well defined. Here, we show, using substrate trapping, that p120 is a direct target of the protein tyrosine phosphatase, PTP-PEST, in epithelial cells. Stable shRNA knockdown of PTP-PEST in colon carcinoma cells results in an increased cytosolic pool of p120 concomitant with its enhanced tyrosine phosphorylation and decreased association with E-cadherin. Consistent with this, PTPPEST knockdown cells exhibit increased motility, enhanced Rac1 and decreased RhoA activity on a collagen substrate. Furthermore, p120 localization is enhanced at actin-rich protrusions and lamellipodia and has an increased association with the guanine nucleotide exchange factor, VAV2, and cortactin. Exchange factor activity of VAV2 is enhanced by PTP-PEST knockdown whereas overexpression of a VAV2 C-terminal domain or DH domain mutant blocks cell motility. Analysis of point mutations identified tyrosine 335 in the N-terminal domain of p120 as the site of PTP-PEST dephosphorylation. A Y335F mutant of p120 failed to induce the 'p120 phenotype', interact with VAV2, stimulate cell motility or activate Rac1. Together, these data suggest that PTP-PEST affects epithelial cell motility by controlling the distribution and phosphorylation of p120 and its availability to control Rho GTPase activity.

Original languageEnglish (US)
Pages (from-to)497-508
Number of pages12
JournalJournal of Cell Science
Volume127
Issue number3
DOIs
StatePublished - Feb 1 2014

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Non-Receptor Type 12 Protein Tyrosine Phosphatase
rho GTP-Binding Proteins
Cell Movement
Tyrosine
Epithelial Cells
Phosphorylation
Cortactin
Guanine Nucleotide Exchange Factors
Adherens Junctions
Pseudopodia
Protein Tyrosine Phosphatases
Cadherins
Point Mutation
Small Interfering RNA
Actins
Colon
Collagen
delta catenin
Carcinoma
Phenotype

Keywords

  • Cell motility
  • p120 catenin
  • PTP
  • Rho GTPase

ASJC Scopus subject areas

  • Cell Biology

Cite this

PTP-PEST targets a novel tyrosine site in p120 catenin to control epithelial cell motility and Rho GTPase activity. / Espejo, Rosario; Jeng, Yowjiun; Paulucci-Holthauzen, Adriana; Rengifo-Cam, William; Honkus, Krysta; Anastasiadis, Panagiotis Z; Sastry, Sarita K.

In: Journal of Cell Science, Vol. 127, No. 3, 01.02.2014, p. 497-508.

Research output: Contribution to journalArticle

Espejo, Rosario ; Jeng, Yowjiun ; Paulucci-Holthauzen, Adriana ; Rengifo-Cam, William ; Honkus, Krysta ; Anastasiadis, Panagiotis Z ; Sastry, Sarita K. / PTP-PEST targets a novel tyrosine site in p120 catenin to control epithelial cell motility and Rho GTPase activity. In: Journal of Cell Science. 2014 ; Vol. 127, No. 3. pp. 497-508.
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