Activation of Cdc42 by trans interactions of the cell adhesion molecules nectins through c-Src and Cdc42-GEF FRG.
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.
Fukuhara
Tatsuro
T
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
Shimizu
Kazuya
K
Kawakatsu
Tomomi
T
Fukuyama
Taihei
T
Minami
Yukiko
Y
Honda
Tomoyuki
T
Hoshino
Takashi
T
Yamada
Tomohiro
T
Ogita
Hisakazu
H
Okada
Masato
M
Takai
Yoshimi
Y
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D051379:Mice; D000075983:Nectins; D011554:Pseudopodia / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D000075983:Nectins; D019061:src-Family Kinases; D020764:cdc42 GTP-Binding Protein