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J. Biol. Chem., Vol. 281, Issue 22, 15423-15433, June 2, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/22/15423    most recent M602607200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yan, H.-X. Articles by Wang, H.-Y. Search for Related Content PubMed PubMed Citation Articles by Yan, H.-X. Articles by Wang, H.-Y. Social Bookmarking                      What's this?

Protein-tyrosine Phosphatase PCP-2 Inhibits -Catenin Signaling and Increases E-cadherin-dependent Cell Adhesion^*

He-Xin Yan, Wen Yang, Rui Zhang, Lei Chen, Liang Tang, Bo Zhai, Shu-Qin Liu, Hui-Fang Cao, Xiao-Bo Man, Hong-Ping Wu, Meng-Chao Wu, and Hong-Yang Wang¹

From the International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438 and the National Laboratory for Oncogene and Related Genes, Cancer Institute of Shanghai Jiao Tong University, Shanghai 200032, China

-Catenin is a key molecule involved in both cell adhesion and Wnt signaling pathway. However, the exact relationship between these two roles has not been clearly elucidated. Tyrosine phosphorylation of -catenin was shown to decrease its binding to E-cadherin, leading to decreased cell adhesion and increased -catenin signaling. We have previously shown that receptor-like protein-tyrosine phosphatase PCP-2 localizes to the adherens junctions and directly binds and dephosphorylates -catenin, suggesting that PCP-2 might regulate the balance between signaling and adhesive -catenin. Here we demonstrate that PCP-2 can inhibit both the wild-type and constitutively active forms of -catenin in activating target genes such as c-myc. The phosphatase activity of PCP-2 is required for this effect since loss of catalytic activity attenuates its inhibitory effect on -catenin activation. Expression of PCP-2 in SW480 colon cancer cells can lead to stabilization of cytosolic pools of -catenin perhaps, by virtue of their physical interaction. PCP-2 expression also leads to increased membrane-bound E-cadherin and greater stabilization of adherens junctions by dephosphorylation of -catenin, which could further sequester cytosolic -catenin and thus inhibit -catenin mediated nuclear signaling. Furthermore, SW480 cells stably expressing PCP-2 have a reduced ability to proliferate and migrate. Thus, PCP-2 may play an important role in the maintenance of epithelial integrity, and a loss of its regulatory function may be an alternative mechanism for activating -catenin signaling.

Received for publication, March 20, 2006

^* This work was supported by grants from the High-Tech Research and Development Program of China (Grant 2001AA221021); China Key Basic Research Program Grant 2002BA711A02-3; and National Natural Science Foundation of China Grant 30370740. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence to: Hong-Yang Wang, M.D. International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, 225 Changhai Road, 200438 Shanghai, China. Tel: 86 21 2507 0856; Fax: 86 21 6556 6851; E-mail: hywangk{at}vip.sina.com.

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