Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion and migration

Hiroshi Matsuoka, Hiroya Obama, Meghan L. Kelly, Toshimitsu Matsui, Masaru Nakamoto

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

EphB6 is a unique member in the Eph family of receptor tyrosine kinases in that its kinase domain contains several alterations in conserved amino acids and is catalytically inactive. Although EphB6 is expressed both in a variety of embryonic and adult tissues, biological functions of this receptor are largely unknown. In the present study, we examined the function of EphB6 in cell adhesion and migration. We demonstrated that EphB6 exerted biphasic effects in response to different concentrations of the ephrin-B2 ligand; EphB6 promoted cell adhesion and migration when stimulated with low concentrations of ephrin-B2, whereas it induced repulsion and inhibited migration upon stimulation with high concentrations of ephrin-B2. A truncated EphB6 receptor lacking the cytoplasmic domain showed monophasic-positive effects on cell adhesion and migration, indicating that the cytoplasmic domain is essential for the negative effects. EphB6 is constitutively associated with the Src family kinase Fyn. High concentrations of ephrin-B2 induced tyrosine phosphorylation of EphB6 through an Src family kinase activity. These results indicate that EphB6 can both positively and negatively regulate cell adhesion and migration, and suggest that tyrosine phosphorylation of the receptor by an Src family kinase acts as the molecular switch for the functional transition.

Original languageEnglish
Pages (from-to)29355-29363
Number of pages9
JournalThe Journal of Biological Chemistry
Volume280
Issue number32
Early online date13 Jun 2005
DOIs
Publication statusPublished - 12 Aug 2005

Keywords

  • regulates integrin activity
  • neural crest migration
  • growth-factor receptor
  • tyrosine kinase
  • autophosphorylation site
  • branch extension
  • cross-linking
  • family
  • protein
  • ligand

Cite this

Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion and migration. / Matsuoka, Hiroshi; Obama, Hiroya; Kelly, Meghan L.; Matsui, Toshimitsu; Nakamoto, Masaru.

In: The Journal of Biological Chemistry, Vol. 280, No. 32, 12.08.2005, p. 29355-29363.

Research output: Contribution to journalArticle

Matsuoka, Hiroshi ; Obama, Hiroya ; Kelly, Meghan L. ; Matsui, Toshimitsu ; Nakamoto, Masaru. / Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion and migration. In: The Journal of Biological Chemistry. 2005 ; Vol. 280, No. 32. pp. 29355-29363.
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