Activation of Cdc42 by trans interactions of the cell adhesion molecules nectins through c-Src and Cdc42-GEF FRG

Tatsuro Fukuhara, Kazuya Shimizu, Tomomi Kawakatsu, Taihei Fukuyama, Yukiko Minami, Tomoyuki Honda, Takashi Hoshino, Tomohiro Yamada, Hisakazu Ogita, Masato Okada, Yoshimi Takai

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)

Abstract

Nectins, Ca2+-independent immunoglobulin-like cell-cell adhesion molecules, initiate cell-cell adhesion by their trans interactions and recruit cadherins to cooperatively form adherens junctions (AJs). In addition, the trans interactions of nectins induce the activation of Cdc42 and Rac small G proteins, which increases the velocity of the formation of AJs. We examined here how nectins induce the activation of Cdc42 in MDCK epithelial cells and L fibroblasts. Nectins recruited and activated c-Src at the nectin-based cell-cell adhesion sites. FRG, a GDP/GTP exchange factor specific for Cdc42, was then recruited there, tyrosine phosphorylated by c-Src, and activated, causing an increase in the GTP-bound active form of Cdc42. Inhibition of the nectin-induced activation of c-Src suppressed the nectin-induced activation of FRG and Cdc42. Inhibition of the nectin-induced activation of FRG or depletion of FRG by RNA interference suppressed the nectin-induced activation of Cdc42. These results indicate that nectins induce the activation of Cdc42 through c-Src and FRG locally at the nectin-based cell-cell adhesion sites.

Original languageEnglish
Pages (from-to)393-405
Number of pages13
JournalJournal of Cell Biology
Volume166
Issue number3
DOIs
Publication statusPublished - Aug 2 2004
Externally publishedYes

Keywords

  • Adherens junctions
  • GDP/GTP exchange factors
  • Intracellular signaling
  • Small G proteins
  • Src family kinases

ASJC Scopus subject areas

  • Cell Biology

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