The regulatory or phosphorylation domain of p120 catenin controls E-cadherin dynamics at the plasma membrane

Fukumoto, Yuri; Shintani, Yasushi; Reynolds, Albert B.; Johnson, Keith R.; Wheelock, Margaret J.

doi:10.1016/j.yexcr.2007.07.024

Cited by 54 publications

(50 citation statements)

References 45 publications

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“…Previous investigations of the roles of p120 catenin subfamily proteins in cell culture and during development show their importance for general cell adhesion and for extension of the vertebrate axis (e.g., Fukumoto et al, 2008;Wildenberg et al, 2006;McCrea and Park, 2007). Our studies show that knockdown of the zygotic expression of p120 catenin d1 in early zebrafish embryos resulted in formation of wider and thinner somites, as well as attenuation of dorsal axial extension.…”

Section: Developmental Dynamicssupporting

confidence: 62%

“…Table S1). The major regulatory phosphorylation sites are between the Met-3 and Met-4 start sites, residues 92 to 324 in the human sequence (Fukumoto et al, 2008). To investigate the ontogeny of the expression of p120 catenin proteins in early development, we ran Western blots using a rabbit polyclonal antibody against a peptide of mouse p120 catenin ( Fig.…”

Section: Results P120 Catenin D1 Is the Most Highly Expressed P120 Camentioning

confidence: 99%

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Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm

Hsu

Muerdter

Knickerbocker

et al. 2012

Developmental Dynamics

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Background: We investigated the roles of p120 catenin, Cdc42, Rac1, and RhoA GTPases in regulating migration of presomitic mesoderm cells in zebrafish embryos. p120 catenin has dual roles: It binds the intracellular and juxtamembrane region of cadherins to stabilize cadherin-mediated adhesion with the aid of RhoA GTPase, and it activates Cdc42 GTPase and Rac1 GTPase in the cytosol to initiate cell motility. Results: During gastrulation of zebrafish embryos, knockdown of the synthesis of zygotic p120 catenind1 mRNAs with a splice-site morpholino caused lateral widening and anterior-posterior shortening of the presomitic mesoderm and somites and a shortened anterior-posterior axis. These phenotypes indicate a cell-migration effect. Co-injection of low amounts of wild-type Cdc42 or wild-type Rac1 or dominant-negative RhoA mRNAs, but not constitutively-active Cdc42 mRNA, rescued these p120 catenin d1-depleted embryos. Conclusions: These downstream small GTPases require appropriate spatiotemporal stimulation or cycling of GTP to guide mesodermal cell migration. A delicate balance of Rho GTPases and p120 catenin underlies normal development. Developmental Dynamics 241:1545-1561, 2012. V C 2012 Wiley Periodicals Inc.Key words: p120 Catenin (CTNND1); ARVCF; Delta-catenin (CTNND2b); Cdc42 GTPase; Rac1 GTPase, RhoA GTPase; gastrulation; presomitic mesoderm; somites; zebrafish Key findings p120 catetin is required for extension of the dorsal axis and normal migration of the presomitic mesoderm. Cdc42 and Rac1 GTPases are downstream of p120 catenin d1 signaling and require exchange of GTP for GDP. Local stimulation of the exchange of GTP for GDP in Cdc42 and Rac GTPases mediates directional migration of the presomitic mesoderm. A balance of the amount of p120 catenin d1 and localized activation or turnover of Cdc42, Rac1, and Rho GTPase are required for normal zebrafish cell migration. Accepted 31 July 2012 Developmental DynamicsABBREVIATIONS Ab antibody ARVCF armadillo repeat gene deleted in velo-cardio-facial syndrome CA constitutively active Chr chromosome C(t) relative amount of RT-PCR product hpf hours post-fertilization DN dominant negative d1 splice-MO antisense morpholino oligonucleotide to the 12 th splice site of zebrafish p120 catenin d1 p120 catenin d1 (CTNND1) also called p120 catenin, Xenopus p120 catenin is a CTNND1 p120 catenin d2b (CTNND2b) also called Delta-catenin Rok1 Rho kinase1 RT reverse transcriptase minus-RT controls without reverse transcriptase qRT-PCR quantitative real-time PCR WT wild-type Xp120 catenin mRNA Xenopus p120 catenin d1 mRNA.Additional Supporting Information may be found in the online version of this article.

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Section: Developmental Dynamicssupporting

confidence: 62%

Section: Results P120 Catenin D1 Is the Most Highly Expressed P120 Camentioning

confidence: 99%

Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm

Hsu

Muerdter

Knickerbocker

et al. 2012

Developmental Dynamics

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“…2A). The bands of p120-catenin became broader and showed slightly slower mobility than those of parental MIA2 cells in the immunoblot analysis, as Fukumoto et al (2008) had earlier described.…”

Section: Resultssupporting

confidence: 77%

“…However, we may have missed some important features of classical cadherins by these studies, since Ecadherin is mainly expressed in epithelial cells, not in fibroblasts. Hence, in the present study we used the epithelial cell line MIA PaCa-2 (MIA2), a pancreatic adenocarcinoma, which does not express classical cadherins, but can support the strong cell adhesion activity of classical cadherins when transfected with them (Fukumoto et al, 2008;Ozaki et al, 2010). In addition, we chose N-cadherin as a model classical cadherin and studied the properties of its cytoplasmic domain by mutagenesis in this study, since N-cadherin is not endocytosed much even in the absence of p120-cateninor β-catenin-binding site (Chen et al, 2003;Ozawa, 2003), thus providing a simpler experimental system for the study of function of the cytoplasmic domain than that of Ecadherin.…”

Section: Introductionmentioning

confidence: 99%

p120-catenin Is Essential for N-cadherin-mediated Formation of Proper Junctional Structure, thereby Establishing Cell Polarity in Epithelial Cells

Ozaki

Yoshioka

Tominaga

et al. 2010

Cell Struct. Funct.

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ABSTRACT. The role of p120-catenin in the function of classical cadherins is still enigmatic despite various studies. To elucidate its role, we examined the effect of p120-catenin on the N-cadherin-mediated localization of junctional proteins in epithelial cells in this study. Cadherin-deficient MIA PaCa-2 epithelial cells did not show linear localization of tight junction proteins ZO-1 and occludin. When N-cadherin was expressed in these cells, however, the resultant transfectant cells revealed strong cell adhesion activity and linear localization of ZO-1, occludin, and N-cadherin in the lateral membrane. When the p120-catenin-binding site of N-cadherin was disrupted, the linear localization of ZO-1 and occludin disappeared, and the mutant N-cadherin became localized more diffusely in the transfectant, although the cell adhesion activity did not change much. Knockdown of p120-catenin also resulted in the very weak localization of ZO-1 and occludin. A similar effect of p120-catenin on the localization of junctional proteins was obtained under more dynamic conditions in a wound healing assay. Moreover, p120-catenin was essential for the regulation of centrosome orientation in this healing assay. Taken together, the present data indicate that p120-catenin is essential for N-cadherin-mediated formation of proper junctional structures and thereby the establishment of the cell polarity. Similar results were obtained when Ecadherin mutants comparable to those of N-cadherin were used, suggesting that p120-catenin plays the same role in the function of other classical cadherins.

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“…The specificities of HECD-1 and 13A9 have been previously demonstrated (56). Anti-DDR1 rabbit antiserum (C-20; immunohistochemistry dilution 1:100, immunoprecipitation dilution 1:100, Western blot dilution 1:1000) was obtained from Santa Cruz Biotechnology, Inc. (Dallas, TX).…”

Section: Methodsmentioning

confidence: 99%

Up-regulation of N-cadherin by Collagen I-activated Discoidin Domain Receptor 1 in Pancreatic Cancer Requires the Adaptor Molecule Shc1

Huang¹,

Svoboda²,

Lazenby³

et al. 2016

Journal of Biological Chemistry

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Pancreatic ductal adenocarcinomas are highly malignant cancers characterized by extensive invasion into surrounding tissues, metastasis to distant organs, and a limited response to therapy. A main feature of pancreatic ductal adenocarcinomas is desmoplasia, which leads to extensive deposition of collagen I. We have demonstrated that collagen I can induce epithelialmesenchymal transition (EMT) in pancreatic cancer cells. A hallmark of EMT is an increase in the expression of the mesenchymal cadherin N-cadherin. Previously we showed up-regulation of N-cadherin promotes tumor cell invasion and that collagen I-induced EMT is mediated by two collagen receptors, ␣2␤1-integrin and discoidin domain receptor 1 (DDR1). DDR1 is a receptor-tyrosine kinase widely expressed during embryonic development and in many adult tissues and is also highly expressed in many different cancers. In the signaling pathway initiated by collagen, we have shown proline-rich tyrosine kinase 2 (Pyk2) is downstream of DDR1. In this study we found isoform b of DDR1 is responsible for collagen I-induced up-regulation of N-cadherin and tyrosine 513 of DDR1b is necessary. Knocking down Shc1, which binds to tyrosine 513 of DDR1b via its PTB (phosphotyrosine binding) domain, eliminates the upregulation of N-cadherin. The signaling does not require a functional SH2 domain or the tyrosine residues commonly phosphorylated in Shc1 but is mediated by the interaction between a short segment of the central domain of Shc1 and the proline-rich region of Pyk2. Taken together, these data illustrate DDR1b, but not DDR1a, mediates collagen I-induced N-cadherin up-regulation, and Shc1 is involved in this process by coupling to both DDR1 and Pyk2.Pancreatic cancer is currently the fourth leading cause of cancer-related mortality in the United States with a 5-year survival rate of ϳ6% (American Cancer Society, 2014). This unfortunate outcome is mainly due to the aggressive behavior of this cancer and the lack of symptoms early in the disease. One of the major features of pancreatic cancer is that during the early stages an extensive stromal reaction occurs called desmoplasia. A dense stroma forms, which consists of myofibroblasts (pancreatic stellate cells), abundant extracellular matrix, and different types of inflammatory cells including macrophages, mast cells, lymphocytes, and plasma cells (1, 2). The extracellular matrix components include collagens, fibronectin, hyaluronic acid, and proteoglycans, whereas the major part is type I collagen (3, 4).The atypical stroma plays many roles in pancreatic cancer. It changes the normal architecture of pancreatic tissue and induces an abnormal configuration of blood and lymphatic vessels resulting in a hypovascular and hypoxic microenvironment. It also presents a barrier to drug delivery and promotes tumor immunologic tolerance (2, 4). Previously, our laboratory showed that collagen I can induce epithelial-mesenchymal transition (EMT) 2 -like changes in pancreatic cancer mediated by two collagen receptors, ␣2␤1-integrin and ...

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The regulatory or phosphorylation domain of p120 catenin controls E-cadherin dynamics at the plasma membrane

Cited by 54 publications

References 45 publications

Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm

Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm

p120-catenin Is Essential for N-cadherin-mediated Formation of Proper Junctional Structure, thereby Establishing Cell Polarity in Epithelial Cells

Up-regulation of N-cadherin by Collagen I-activated Discoidin Domain Receptor 1 in Pancreatic Cancer Requires the Adaptor Molecule Shc1

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