Involvement of the c-Src-Crk-C3G-Rap1 signaling in the nectin-induced activation of Cdc42 and formation of adherens junctions.
Nectins, Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules, induce the activation of Cdc42 and Rac small G proteins, enhancing the formation of cadherin-based adherens junctions (AJs) and claudin-based tight junctions. Nectins recruit and activate c-Src at the nectin-based cell-cell contact sites. c-Src then activates Cdc42 through FRG, a Cdc42-GDP/GTP exchange factor. We showed here that Rap1 small G protein was involved in the nectin-induced activation of Cdc42 and formation of AJs. Rap1 was recruited to the nectin-based cell-cell contact sites and locally activated through the c-Src-Crk-C3G signaling there. The activation of either c-Src or Rap1 alone was insufficient for and the activation of both molecules was essential for the activation of FRG. The activation of Rap1 was not necessary for the c-Src-mediated phosphorylation or recruitment of FRG. The inhibition of the Crk, C3G, or Rap1 signaling reduced the formation of AJs. These results indicate that Rap1 is activated by nectins through the c-Src-Crk-C3G signaling and involved in the nectin-induced, c-Src- and FRG-mediated activation of Cdc42 and formation of AJs.
Fukuyama
Taihei
T
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Ogita
Hisakazu
H
Kawakatsu
Tomomi
T
Fukuhara
Tatsuro
T
Yamada
Tomohiro
T
Sato
Tatsuhiro
T
Shimizu
Kazuya
K
Nakamura
Takeshi
T
Matsuda
Michiyuki
M
Takai
Yoshimi
Y
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004285:Dogs; D004789:Enzyme Activation; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000378:metabolism; D000075983:Nectins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*; D019061:src-Family Kinases
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D020735:Guanine Nucleotide-Releasing Factor 2; D000075983:Nectins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D020764:cdc42 GTP-Binding Protein; D020827:rap1 GTP-Binding Proteins