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Association of Dishevelled with Eph tyrosine kinase receptor and ephrin mediates cell repulsion
Author(s) -
Tanaka Masamitsu,
Kamo Takaharu,
Ota Satoshi,
Sugimura Haruhiko
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg088
Subject(s) - ephrin , erythropoietin producing hepatocellular (eph) receptor , rhoa , dishevelled , biology , microbiology and biotechnology , eph receptor a2 , receptor tyrosine kinase , tyrosine kinase , signal transduction , xenopus , receptor , receptor protein tyrosine kinases , biochemistry , wnt signaling pathway , frizzled , gene
Eph tyrosine kinase receptors and their membrane‐bound ligands, ephrins, are presumed to regulate cell–cell interactions. The major consequence of bidirectional activation of Eph receptors and ephrin ligands is cell repulsion. In this study, we discovered that Xenopus Dishevelled (Xdsh) forms a complex with Eph receptors and ephrin‐B ligands and mediates the cell repulsion induced by Eph and ephrin. In vitro re‐aggregation assays with Xenopus animal cap explants revealed that co‐expression of a dominant‐negative mutant of Xdsh affected the sorting of cells expressing EphB2 and those expressing ephrin‐B1. Co‐expression of Xdsh induced the activation of RhoA and Rho kinase in the EphB2‐overexpressed cells and in the cells expressing EphB2‐stimulated ephrin‐B1. Therefore, Xdsh mediates both forward and reverse signaling of EphB2 and ephrin‐B1, leading to the activation of RhoA and its effector protein Rho kinase. The inhibition of RhoA activity in animal caps significantly prevents the EphB2‐ and ephrin‐B1‐mediated cell sorting. We propose that Xdsh, which is expressed in various tissues, is involved in EphB and ephrin‐B signaling related to regulation of cell repulsion via modification of RhoA activity.