Cortactin tyrosine phosphorylation at E-cadherin junctions: a switch for epithelium formation through regulation of RhoA

2017 ◽  
Author(s):  
Xuan Liang
Keyword(s):  
Tyrosine Phosphorylation ◽  
Cortactin Tyrosine Phosphorylation ◽  
E Cadherin

scholarly journals PTP1B Regulates Cortactin Tyrosine Phosphorylation by Targeting Tyr446

2008 ◽  
Vol 283 (23) ◽  
pp. 15740-15746 ◽  
Author(s):  
Matthew Stuible ◽  
Nadia Dubé ◽  
Michel L. Tremblay
Keyword(s):  
Tyrosine Phosphorylation ◽  
Cortactin Tyrosine Phosphorylation

Tyrosine phosphorylation of p120(ctn) in v-Src transfected L cells depends on its association with E-cadherin and reduces adhesion activity

2001 ◽  
Vol 114 (3) ◽  
pp. 503-512 ◽  
Author(s):  
M. Ozawa ◽  
T. Ohkubo
Keyword(s):  
Cell Adhesion ◽  
Complex Formation ◽  
Tyrosine Phosphorylation ◽  
Chimeric Protein ◽  
Single Amino Acid ◽  
Membrane Localization ◽  
Wild Type ◽  
L Cells ◽  
Adhesion Activity ◽  
E Cadherin

Cadherins are transmembrane glycoproteins involved in Ca2+-dependent cell-cell adhesion. Using L cells expressing one of three functional E-cadherin constructs, the wild-type, a chimeric molecule with alpha-catenin (EalphaC), and a tail-less one, we determined the effect of v-Src expression on E-cadherin-mediated adhesion. The aggregation of L cells expressing the wild-type or EalphaC chimeric protein, which both interact with p120(ctn), was reduced by v-Src expression, whereas that of L cells expressing the tail-less E-cadherin was not affected by the expression. Tyrosine phosphorylation of p120(ctn) was observed in v-Src-transformed L cells expressing the wild-type or EalphaC chimeric protein, but not in ones expressing the tail-less E-cadherin. Thus, tyrosine phosphorylation of p120(ctn) depends on the complex formation with E-cadherin and the resulting membrane localization. Constitutive phosphorylation of p120(ctn) on serine and threonine residues also depends on the complex formation and membrane localization. Coexpression of the p120(ctn) protein with an N-terminal deletion, which eliminates some potential tyrosine phosphorylation sites, or the protein with a single amino acid substitution (tyrosine at 217 to phenylalanine) resulted in an increase in the aggregation of v-Src-transformed EL and EalphaCL cells. These results indicate that tyrosine phosphorylation of p120(ctn) is involved in the v-Src modulation of E-cadherin-mediated cell adhesion.

The homeodomain transcription factors Cdx1 and Cdx2 induce E-cadherin adhesion activity by reducing β- and p120-catenin tyrosine phosphorylation

2007 ◽  
Vol 293 (1) ◽  
pp. G54-G65 ◽  
Author(s):  
Toshihiko Ezaki ◽  
Rong-Jun Guo ◽  
Hong Li ◽  
Albert B. Reynolds ◽  
John P. Lynch
Keyword(s):  
Transcription Factors ◽  
Cell Adhesion ◽  
Tyrosine Phosphorylation ◽  
Intestinal Cell ◽  
Specific Gene ◽  
P120 Catenin ◽  
Cdx2 Expression ◽  
E Cadherin ◽  
Cell Cell ◽  
Homeodomain Transcription Factors

The homeodomain transcription factors Cdx1 and Cdx2 are regulators of intestine-specific gene expression. They also regulate intestinal cell differentiation and proliferation; however, these effects are poorly understood. Previously, we have shown that expression of Cdx1 or Cdx2 in human Colo 205 cells induces a mature colonocyte morphology characterized by the induction of a polarized, columnar shape with apical microvilli and strong cell-cell adhesion. To elucidate the mechanism underlying this phenomenon, we investigated the adherens junction complex. Cdx1 or Cdx2 expression reduced Colo 205 cell migration and invasion in vitro, suggesting a physiologically significant change in cadherin function. However, Cdx expression did not significantly effect E-cadherin, α-, β-, or γ-catenin, or p120-catenin protein levels. Additionally, no alteration in their intracellular distribution was observed. Cdx expression did not alter the coprecipitation of β-catenin with E-cadherin; however, it did reduce p120-catenin-E-cadherin coprecipitation. Tyrosine phosphorylation of β- and p120-catenin is known to disrupt E-cadherin-mediated cell adhesion and is associated with robust p120-catenin/E-cadherin interactions. We specifically investigated β- and p120-catenin for tyrosine phosphorylation and found that it was significantly diminished by Cdx1 or Cdx2 expression. We restored β- and p120-catenin tyrosine phosphorylation in Cdx2-expressing cells by knocking down the expression of protein tyrosine phosphatase 1B and noted a significant decline in cell-cell adhesion. We conclude that Cdx expression in Colo 205 cells induces E-cadherin-dependent cell-cell adhesion by reducing β- and p120-catenin tyrosine phosphorylation. Ascertaining the mechanism for this novel Cdx effect may improve our understanding of the regulation of cell-cell adhesion in the colonic epithelium.

scholarly journals Platelet-activating factor increases mucosal permeability in rat intestine via tyrosine phosphorylation of E-cadherin

2000 ◽  
Vol 129 (7) ◽  
pp. 1522-1529 ◽  
Author(s):  
Xiao-Di Tan ◽  
Hong Chang ◽  
Xiao-Wu Qu ◽  
Michael Caplan ◽  
Frank Gonzalez-Crussi ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Platelet Activating Factor ◽  
Rat Intestine ◽  
Mucosal Permeability ◽  
E Cadherin

scholarly journals The Addition of BisectingN-Acetylglucosamine Residues to E-cadherin Down-regulates the Tyrosine Phosphorylation of β-Catenin

2000 ◽  
Vol 276 (1) ◽  
pp. 475-480 ◽  
Author(s):  
Takatoshi Kitada ◽  
Eiji Miyoshi ◽  
Katsuhisa Noda ◽  
Shigeki Higashiyama ◽  
Hideyuki Ihara ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
E Cadherin

scholarly journals Actin depolymerization-induced tyrosine phosphorylation of cortactin: the role of Fer kinase

2004 ◽  
Vol 380 (2) ◽  
pp. 581-591 ◽  
Author(s):  
Lingzhi FAN ◽  
Caterina Di CIANO-OLIVEIRA ◽  
Scott A. WEED ◽  
Andrew W. B. CRAIG ◽  
Peter A. GREER ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Feedback Mechanism ◽  
Reciprocal Relationship ◽  
Actin Binding ◽  
Hypertonic Stress ◽  
Tyrosine Residues ◽  
Actin Depolymerization ◽  
N Terminus ◽  
Cortactin Tyrosine Phosphorylation

The F-actin-binding protein cortactin is an important regulator of cytoskeletal dynamics, and a prominent target of various tyrosine kinases. Tyrosine phosphorylation of cortactin has been suggested to reduce its F-actin cross-linking capability. In the present study, we investigated whether a reciprocal relationship exists, i.e. whether the polymerization state of actin impacts on the cortactin tyrosine phosphorylation. Actin depolymerization by LB (latrunculin B) induced robust phosphorylation of C-terminal tyrosine residues of cortactin. In contrast, F-actin stabilization by jasplakinolide, which redistributed cortactin to F-actin-containing patches, prevented cortactin phosphorylation triggered by hypertonic stress or LB. Using cell lines deficient in candidate tyrosine kinases, we found that the F-actin depolymerization-induced cortactin phosphorylation was mediated by the Fyn/Fer kinase pathway, independent of Src and c-Abl. LB caused modest Fer activation and strongly facilitated the association between Fer and cortactin. Interestingly, the F-actin-binding region within the cortactin N-terminus was essential for the efficient phosphorylation of C-terminal tyrosine residues. Investigating the structural requirements for the Fer–cortactin association, we found that (i) phosphorylation-incompetent cortactin still bound to Fer; (ii) the isolated N-terminus associated with Fer; and (iii) the C-terminus alone was insufficient for binding. Thus the cortactin N-terminus participates in the Fer–cortactin interaction, which cannot be fully due to the binding of the Fer Src homology 2 domain to C-terminal tyrosine residues of cortactin. Taken together, F-actin stabilization prevents cortactin tyrosine phosphorylation, whereas depolymerization promotes it. Depolymerization-induced phosphorylation is mediated by Fer, and requires the actin-binding domain of cortactin. These results define a novel F-actin-dependent pathway that may serve as a feedback mechanism during cytoskeleton remodelling.

scholarly journals Dynamic Interaction of PTPμ with Multiple Cadherins In Vivo

1998 ◽  
Vol 141 (1) ◽  
pp. 287-296 ◽  
Author(s):  
Susann M. Brady-Kalnay ◽  
Tracy Mourton ◽  
Joseph P. Nixon ◽  
Gregory E. Pietz ◽  
Michael Kinch ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Tyrosine Phosphatase ◽  
Cross Reactivity ◽  
Receptor Protein ◽  
Temperature Sensitive ◽  
Mutant Form ◽  
Cell Biol ◽  
E Cadherin

There is a growing body of evidence to implicate reversible tyrosine phosphorylation as an important mechanism in the control of the adhesive function of cadherins. We previously demonstrated that the receptor protein tyrosine phosphatase PTPμ associates with the cadherin–catenin complex in various tissues and cells and, therefore, may be a component of such a regulatory mechanism (Brady-Kalnay, S.M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977– 986). In this study, we present further characterization of this interaction using a variety of systems. We observed that PTPμ interacted with N-cadherin, E-cadherin, and cadherin-4 (also called R-cadherin) in extracts of rat lung. We observed a direct interaction between PTPμ and E-cadherin after coexpression in Sf9 cells. In WC5 cells, which express a temperature-sensitive mutant form of v-Src, the complex between PTPμ and E-cadherin was dynamic, and conditions that resulted in tyrosine phosphorylation of E-cadherin were associated with dissociation of PTPμ from the complex. Furthermore, we have demonstrated that the COOH-terminal 38 residues of the cytoplasmic segment of E-cadherin was required for association with PTPμ in WC5 cells. Zondag et al. (Zondag, G., W. Moolenaar, and M. Gebbink. 1996. J. Cell Biol. 134: 1513–1517) have asserted that the association we observed between PTPμ and the cadherin–catenin complex in immunoprecipitates of the phosphatase arises from nonspecific cross-reactivity between BK2, our antibody to PTPμ, and cadherins. In this study we have confirmed our initial observation and demonstrated the presence of cadherin in immunoprecipitates of PTPμ obtained with three antibodies that recognize distinct epitopes in the phosphatase. In addition, we have demonstrated directly that the anti-PTPμ antibody BK2 that we used initially did not cross-react with cadherin. Our data reinforce the observation of an interaction between PTPμ and E-cadherin in vitro and in vivo, further emphasizing the potential importance of reversible tyrosine phosphorylation in regulating cadherin function.

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