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EMBO J February 17, 2003; 22 (4): 847-58.

Association of Dishevelled with Eph tyrosine kinase receptor and ephrin mediates cell repulsion.

Tanaka M , Kamo T , Ota S , Sugimura H .

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.

PubMed ID: 12574121
PMC ID: PMC145448
Article link: EMBO J

Genes referenced: dvl1 dvl2 ephb2 rho.2 rhoa

References [+] :
Brückner, Tyrosine phosphorylation of transmembrane ligands for Eph receptors. 1997, Pubmed

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