Association of Dishevelled With Eph Tyrosine Kinase Receptor and Ephrin Mediates Cell Repulsion

EMBO J. 2003 Feb 17;22(4):847-58. doi: 10.1093/emboj/cdg088.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Dishevelled Proteins
  • Ephrins / metabolism*
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Eph Family / metabolism*
  • Rhombencephalon / embryology
  • Rhombencephalon / metabolism
  • Xenopus / embryology
  • Xenopus Proteins
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • DVL1 protein, Xenopus
  • Dishevelled Proteins
  • Ephrins
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Xenopus Proteins
  • Receptors, Eph Family
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein