p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction.
beta-Catenin has a key role in the formation of adherens junction through its interactions with E-cadherin and alpha-catenin. We show here that interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins. We have also examined whether these kinases are involved in the regulation of this interaction by K-ras. Stable transfectants of the K-ras oncogene in intestinal epithelial IEC18 cells were generated which show little alpha-catenin-beta-catenin association with respect to control clones; this effect is accompanied by increased Tyr-142 phosphorylation and activation of Fer and Fyn kinases. As reported for Fer, Fyn kinase is constitutively bound to p120 catenin; expression of K-ras induces the phosphorylation of p120 catenin on tyrosine residues increasing its affinity for E-cadherin and, consequently, promotes the association of Fyn with the adherens junction complex. Yes tyrosine kinase also binds to p120 catenin but only upon activation, and stimulates Fer and Fyn tyrosine kinases. These results indicate that p120 catenin acts as a docking protein facilitating the activation of Fer/Fyn tyrosine kinases by Yes and demonstrate the role of these p120 catenin-associated kinases in the regulation of beta-catenin-alpha-catenin interaction.
Piedra
Jose
J
Unitat de Biofísica, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain.
Miravet
Susana
S
Castaño
Julio
J
Pálmer
Héctor G
HG
Heisterkamp
Nora
N
García de Herreros
Antonio
A
Duñach
Mireia
M
D000818:Animals; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D051381:Rats; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D051178:alpha Catenin; D051176:beta Catenin; D019061:src-Family Kinases; D000095002:Delta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D051177:Catenins; D015815:Cell Adhesion Molecules; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; C052602:proto-oncogene protein c-fes-fps; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D019061:src-Family Kinases; D000095002:Delta Catenin