title: Physical and functional interaction between receptor-like protein tyrosine phosphatase PCP-2 and beta-catenin.
abstract: We have previously identified a human receptor protein tyrosine phosphatase of the MAM domain family, termed PCP-2, in human pancreatic adenocarcinoma cells and found that this protein was colocalized with beta-catenin and E-cadherin at cell junctions [Wang, H.-Y., et al. (1996) Oncogene 12, 2555-2562]. Its intracellular part consists of two tandem phosphatase domains and a relatively large juxtamembrane region that is homologous to the conserved intracellular domain of cadherins, suggesting a role in the regulation of cell adhesion. This study reports that PCP-2 was endogenously expressed at the cell surface and upregulated with increased cell density. An in vivo binding assay revealed that PCP-2 could directly interact with beta-catenin through a region in the juxtamembrane domain. Tyrosine phosphorylation of beta-catenin by EGF or active SrcY527F did not disrupt the formation of the PCP-2-beta-catenin complex, while PCP-2 in this complex could cause a significant reduction in the phosphorylation level in beta-catenin. Finally, we showed that PCP-2 was a negative regulator for cell migration. In conclusion, interaction of PCP-2 with its substrate beta-catenin is involved in the process of cell-cell contact.
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, 225 Changhai Road, Shanghai 200438, People's Republic of China.
authors.forename: He-Xin
authors.initials: HX
authors.lastname: Yan
authors.forename: Ya-Qin
authors.initials: YQ
authors.lastname: He
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Jin-Zhang
authors.initials: JZ
authors.lastname: Zeng
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Cao
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Wu
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000502:physiology; D019556:COS Cells; D015820:Cadherins / Q000737:chemistry* / Q000502:physiology; D002452:Cell Count; D002460:Cell Line; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D013379:Substrate Specificity / Q000235:genetics; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D014443:Tyrosine / Q000737:chemistry; D051176:beta Catenin
chemical_list: D000951:Antigens, Neoplasm; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D051176:beta Catenin; C055984:mammary carcinoma antigen; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases