V-src kinase shifts the cadherin-based cell adhesion from the strong to the weak state and beta catenin is not required for the shift.
The elevation of tyrosine phosphorylation level is thought to induce the dysfunction of cadherin through the tyrosine phosphorylation of beta catenin. We evaluated this assumption using two cell lines. First, using temperature-sensitive v-src-transfected MDCK cells, we analyzed the modulation of cadherin-based cell adhesion by tyrosine phosphorylation. Cell aggregation and dissociation assays at nonpermissive and permissive temperatures indicated that elevation of the tyrosine phosphorylation does not totally affect the cell adhesion ability of cadherin but shifts it from a strong to a weak state. The tyrosine phosphorylation levels of beta catenin, ZO-1, ERM (ezrin/radixin/moesin), but not alpha catenin, vinculin, and alpha-actinin, were elevated in the weak state. To evaluate the involvement of the tyrosine phosphorylation of beta catenin in this shift of cadherin-based cell adhesion, we introduced v-src kinase into L fibroblasts expressing the cadherin-alpha catenin fusion protein, in which beta catenin is not involved in cell adhesion. The introduction of v-src kinase in these cells shifted their adhesion from a strong to a weak state. These findings indicated that the tyrosine phosphorylation of beta catenin is not required for the strong-to-weak state shift of cadherin-based cell adhesion, but that the tyrosine phosphorylation of other junctional proteins, ERM, ZO-1 or unidentified proteins is involved.
Takeda
H
H
Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
Nagafuchi
A
A
Yonemura
S
S
Tsukita
S
S
Behrens
J
J
Birchmeier
W
W
Tsukita
S
S
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D002460:Cell Line / Q000201:enzymology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004285:Dogs; D007686:Kidney Tubules, Distal / Q000166:cytology; D051379:Mice; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013696:Temperature; D015534:Trans-Activators; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051176:beta Catenin; D014443:Tyrosine; D015688:Oncogene Protein pp60(v-src)