Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes.

Abstract

Abstract. p120 was originally identified as a substrate of pp6@ ~ and several receptor tyrosine kinases, but its function is not known. Recent studies revealed that this protein shows homology to a group of proteins, ~-catenln/Armadillo and plakoglobin (,y-catenin), which are associated with the cell adhesion molecules cadherins. In this study, we examined whether p120 is associated with E-cadherin using the human carcinoma cell line HT29, as well as other cell lines, which express both of these proteins. When proteins that copurified with E-cadherin were analyzed, not only ot-catenin, ~catenin, and plakoglobin but also p120 were detected. Conversely, immunoprecipitates of p120 contained E-cadherin and all the catenins, although a large subpopulation of p120 was not associated with E-cadherin. Analysis of these immunoprecipitates suggests that 20% or less of the extractable E-cadherin is associated with p120. When p120 immunoprecipitation was performed with cell lysates depleted of E-cadherin, fl-catenin was no longer coprecipitated, and the amount of plakoglobin copurified was greatly reduced. This finding suggests that there are various forms of t)120 complexes, including pl20/E-cadherin//~-catenin and pl20/E-cadherin/plakoglobin complexes; this association profile contrasts with the mutually exclusive association of/~-catenin and plakoglobin with cadherins. When the COOH-terminal catenin binding site was truncated from E-cadherin, not only/~-catenin but also p120 did not coprecipitate with this mutated E-cadherin. Immunocytological studies showed that p120 colocalized with E-cadherin at cell-cell contact sites, even after non-ionic detergent extraction. Treatment of cells with hepatocyte growth factor/scatter factor altered the level of tyrosine phosphorylation of p120 as well as of/3-catenin and plakoglobin. These results suggest that pl20 associates with E-cadherin at its COOH-terminal region, but the mechanism for this association differs from that for the association of/~-catenin and plakoglobin with E-cadherin, and thus, that p120, whose function could be modulated by growth factors, may play a unique role in regulation of the cadherin-catenin adhesion system.

p120 and Kaiso RegulateHelicobacter pylori-induced Expression of Matrix Metalloproteinase-7

“…p120 can regulate Ecadherin, a cell-cell adhesion molecule that functions as a component of the adherens junction of epithelial tissues, and turnover of E-cadherin is regulated by binding of p120 to the cadherin juxtamembrane domain (Reynolds et al, 1989;Reynolds et al, 1992Reynolds et al, , 1994Shibamoto et al, 1995;Staddon et al, 1995;Anastasiadis et al, 2000;Thoreson et al, 2000;Anastasiadis and Reynolds, 2001;Ireton et al, 2002;Davis et al, 2003;Reynolds and Carnahan, 2004). Studies have demonstrated that loss of E-cadherin or overexpression of p120 results in mislocalization of p120 to the cytoplasm (Reynolds and Carnahan, 2004), where it induces a range of morpho- Figure 7.…”

“…A host molecule that has been implicated in regulation of MMP-7 expression is p120-catenin (p120). p120 was originally identified as a substrate for Src-and receptor-tyrosine kinases (Reynolds et al, 1989(Reynolds et al, , 1992Reynolds and Carnahan, 2004) and is a member of the catenin (ctn) family, an Armadillo domain protein subfamily whose members interact with the cadherin cytoplasmic tail and modulate cadherin function (Reynolds et al, 1994;Shibamoto et al, 1995;Staddon et al, 1995;Reynolds and Carnahan, 2004). Aberrant redistribution of p120 has been observed in several epithelial malignancies, including gastric cancer (Jawhari et al, 1999;Karatzas et al, 1999;Karayiannakis et al, 1999;Thoreson and Reynolds, 2002;Mayerle et al, 2003).…”

Involvement of Cdc42 small G protein in cell-cell adhesion, migration and morphology of MDCK cells

“…At adherens junction, cadherins interact with each other at the extracellular surface and serve as adhesion molecules (for reviews, see Geiger and Ginsberg, 1991;Tsukita et al, 1992;Takeichi, 1995). Cadherins indirectly interact at the cytoplasmic region with the actin cytoskeleton through many peripheral membrane proteins, including a-, b-, and g-catenins, p120, a-actinin, vinculin, neurabin, and afadin (Vestweber and Kemler, 1984;Peyrieras et al, 1985;Ozawa et al, 1989;Shibamoto et al, 1995;Nakanishi et al, 1997;Mandai et al, 1997). Tight junction also plays an important role in the formation of cell polarity and barrier (for reviews, see Schneeberger and Lynch, 1992;Gumbiner, 1993;Anderson and Van Itallie, 1995).…”

Luteinising hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline

“…Similarly, a reduction in E-cadherin often results in b-catenin degradation (Liu et al, 2002). Another protein associated with E-cadherin, p120 (Thoreson et al, 2000), is phosphorylated on both tyrosine and serine residues in response to a variety of growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and colony stimulating factor (CSF)-1, suggesting involvement in active signalling (Downing and Reynolds, 1991;Shibamoto et al, 1995). Thus, cell -cell adhesion serves not only a structural role but dictates cellular behaviour.…”