Published online 3 January 2002. doi:10.1083/jcb.200105140
© The Rockefeller University Press,
0021-9525/2002/1/137 $5.00
The Journal of Cell Biology, Volume 156, Number 1, January 7, 2002 137-148
Fyn tyrosine kinase is a downstream mediator of Rho/PRK2 function in keratinocyte cellcell adhesion
Enzo Calautti,
Maddalena Grossi,
Cristina Mammucari,
Yumi Aoyama,
Maria Pirro,
Yoshitaka Ono,
Jie Li and
G. Paolo Dotto
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129
Address correspondence to G. Paolo Dotto, Cutaneous Biology Research Center, Harvard Medical School, Massachusetts General Hospital, Bldg. 149, 13th St., Charlestown, MA 02129-2060. Tel.: (617) 724-9538. Fax: (612) 724-9572. E-mail: paolo.dotto{at}cbrc2.mgh.harvard.edu
The Rho GTPase and Fyn tyrosine kinase have been implicated previously in positive control of keratinocyte cellcell adhesion. Here, we show that Rho and Fyn operate along the same signaling pathway. Endogenous Rho activity increases in differentiating keratinocytes and is required for both Fyn kinase activation and increased tyrosine phosphorylation of ß- and
-catenin, which is associated with the establishment of keratinocyte cellcell adhesion. Conversely, expression of constitutive active Rho is sufficient to promote cellcell adhesion through a tyrosine kinase- and Fyn-dependent mechanism, trigger Fyn kinase activation, and induce tyrosine phosphorylation of ß- and
-catenin and p120ctn. The positive effects of activated Rho on cellcell adhesion are not induced by an activated Rho mutant with defective binding to the serine/threonine PRK2/PKN kinases. Endogenous PRK2 kinase activity increases with keratinocyte differentiation, and, like activated Rho, increased PRK2 activity promotes keratinocyte cellcell adhesion and induces tyrosine phosphorylation of ß- and
-catenin and Fyn kinase activation. Thus, these findings reveal a novel role of Fyn as a downstream mediator of Rho in control of keratinocyte cellcell adhesion and implicate the PRK2 kinase, a direct Rho effector, as a link between Rho and Fyn activation.
Key Words: E-cadherin; ß- and
-catenin; p120Ctn; PKN/PRK2; adherens junctions

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