Gα(12) binds to the N-terminal regulatory domain of p120(ctn), and downregulates p120(ctn) tyrosine phosphorylation induced by Src family kinases via a RhoA independent mechanism.
p120 Catenin (p120(ctn)) regulates cadherin stability, and thus facilitates strong cell-cell adhesion. Previously, we demonstrated that Gα(12) interacts with p120(ctn). In the present study, we have delineated a region of p120(ctn) that binds to Gα(12). We report that the N-terminal region of p120(ctn) (amino acids 1-346) is necessary and sufficient for the interaction. While the coiled-coiled domain and a charged region, comprising a.a 102-120, were found to be dispensable, amino acids 121-323 were required for p120(ctn) binding to Gα(12). This region harbors the phosphorylation domain of p120(ctn) and has been postulated as important for RhoA regulation. Downregulation of Src family kinase-induced tyrosine phosphorylation of p120(ctn) was observed in the presence of activated Gα(12). This down-regulation was triggered by three different Gα(12) mutants uncoupled from RhoA signalling. Furthermore, a dominant active form of RhoA did not reduce Src-induced phosphoryaltion of p120(ctn). In summary, our results suggest that Gα(12) binds to p120(ctn) and modulates its phosphorylation status through a Rho-independent mechanism. Gα(12) emerges as an important regulator of p120(ctn) function, and possibly of cadherin-mediated adhesion and/or cell motility.
Department of Biomedicine, University of Bergen, Bergen, Norway.
Vandana V
VV
Ardawatia
Miriam
M
Masià-Balagué
Beate F
BF
Krakstad
Bente B
BB
Johansson
Kelly M
KM
Kreitzburg
Endy
E
Spriet
Aurélia E
AE
Lewis
Thomas E
TE
Meigs
Anna M
AM
Aragay
D001665:Binding Sites; D051177:Catenins / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014443:Tyrosine / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*; D000095002:Delta Catenin
D051177:Catenins; D014443:Tyrosine; D019061:src-Family Kinases; D051960:GTP-Binding Protein alpha Subunit, Gi2; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin; C000722347:CTNND1 protein, human