title: p120 serine and threonine phosphorylation is controlled by multiple ligand-receptor pathways but not cadherin ligation.
abstract: p120-catenin (p120) regulates cadherin turnover and is required for cadherin stability. Extensive and dynamic phosphorylation on tyrosine, serine and threonine residues in the N-terminal regulatory domain has been postulated to regulate p120 function, possibly through modulation of the efficiency of p120/cadherin interaction. Here we have utilized novel phospho-specific monoclonal antibodies to four major p120 serine and threonine phosphorylation sites to monitor individual phosphorylation events and their consequences. Surprisingly, membrane-localization and not cadherin interaction is the main determinant in p120 serine and threonine phosphorylation and dephosphorylation. Furthermore, the phospho-status of these four residues had no obvious effect on p120's role in cadherin complex stabilization or cell-cell adhesion. Interestingly, dephosphorylation was dramatically induced by PKC activation, but PKC-independent pathways were also evident. The data suggest that p120 dephosphorylation at these sites is modulated by multiple cell surface receptors primarily through PKC-dependent pathways, but these changes do not seem to reduce p120/cadherin affinity.
authors.affiliation: Department of Cancer Biology, Vanderbilt University Medical Center, 771 Preston Research Building, Nashville, TN 37232, USA.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Xia
authors.forename: Robert H
authors.initials: RH
authors.lastname: Carnahan
authors.forename: Meredith H
authors.initials: MH
authors.lastname: Vaughan
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Wildenberg
authors.forename: Albert B
authors.initials: AB
authors.lastname: Reynolds
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004285:Dogs; D006801:Humans; D008024:Ligands; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D008024:Ligands; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D013912:Threonine; D012694:Serine; D011493:Protein Kinase C; D000095002:Delta Catenin