Tyrosine phosphorylation of p120(ctn) in v-Src transfected L cells depends on its association with E-cadherin and reduces adhesion activity.
Cadherins are transmembrane glycoproteins involved in Ca2+-dependent cell-cell adhesion. Using L cells expressing one of three functional E-cadherin constructs, the wild-type, a chimeric molecule with alpha-catenin (EalphaC), and a tail-less one, we determined the effect of v-Src expression on E-cadherin-mediated adhesion. The aggregation of L cells expressing the wild-type or EalphaC chimeric protein, which both interact with p120(ctn), was reduced by v-Src expression, whereas that of L cells expressing the tail-less E-cadherin was not affected by the expression. Tyrosine phosphorylation of p120(ctn) was observed in v-Src-transformed L cells expressing the wild-type or EalphaC chimeric protein, but not in ones expressing the tail-less E-cadherin. Thus, tyrosine phosphorylation of p120(ctn) depends on the complex formation with E-cadherin and the resulting membrane localization. Constitutive phosphorylation of p120(ctn) on serine and threonine residues also depends on the complex formation and membrane localization. Coexpression of the p120(ctn) protein with an N-terminal deletion, which eliminates some potential tyrosine phosphorylation sites, or the protein with a single amino acid substitution (tyrosine at 217 to phenylalanine) resulted in an increase in the aggregation of v-Src-transformed EL and EalphaCL cells. These results indicate that tyrosine phosphorylation of p120(ctn) is involved in the v-Src modulation of E-cadherin-mediated cell adhesion.
Ozawa
M
M
Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan. mozawa@m.kufm.kagoshima-u.ac.jp
Ohkubo
T
T
D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D051379:Mice; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D010750:Phosphoproteins; D013912:Threonine; D014443:Tyrosine; D012694:Serine; D015688:Oncogene Protein pp60(v-src); D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse