Cancer Sci 2005,
PMID: 16128743
Sato, Tatsuhiro; Irie, Kenji; Okamoto, Ryoko; Ooshio, Takako; Fujita, Naoyuki; Takai, Yoshimi
Nectin is a Ca2+-independent Ig-like cell-cell adhesion molecule that forms homo- and hetero-trans-dimers (trans-interaction). Nectin first forms cell-cell adhesions and then recruits cadherin to the nectin-based cell-cell adhesion sites to form AJ cooperatively with cadherin. In addition, the trans-interaction of nectin and nectin induces the activation of Cdc42 and Rac small G proteins, which enhances the formation of AJ. The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1, a Cdc42-GEF, FRG, and a Rac-GEF, Vav2. Necl-5/Tage4/PVR/CD155 is another Ca2+-independent Ig-like molecule, which does not homophilically trans-interact, but heterophilically trans-interacts with nectin-3, one member of the nectin family. We show here that the trans-interaction of Necl-5 and nectin-3 bidirectionally induces the activation of Cdc42 and Rac. Similarly to the activation of Cdc42 and Rac by the trans-interaction of nectin and nectin, the trans-interaction of Necl-5 and nectin-3 first recruits and activates c-Src at the Necl-5/nectin-3-based cell-cell contact sites. c-Src then phosphorylates FRG and Vav2, and the tyrosine-phosphorylated FRG and Vav2 are recruited to the Necl-5/nectin-3-based cell-cell contact sites. The trans-interaction of Necl-5 and nectin-3 also activates Rap1 through C3G, a Rap-GEF, and this activation of Rap1 is required for the activation of Cdc42 and Rac. These results indicate that the trans-interactions of Necl-5 and nectin-3 and of nectin and nectin induce the activation of Cdc42 and Rac through the common signaling molecules c-Src, Rap1, FRG, and Vav2.
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Text Mining Data
Cdc42 → c-Src: "
The activation of
Cdc42 and Rac by the trans-interaction of nectin and nectin is
mediated by
c-Src , another small G protein, Rap1, a Cdc42-GEF, FRG, and a Rac-GEF, Vav2
"
Cdc42 → Rap1: "
The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1 , a Cdc42-GEF, FRG, and a Rac-GEF, Vav2
"
Cdc42 → Cdc42-GEF: "
The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1, a Cdc42-GEF , FRG, and a Rac-GEF, Vav2
"
Cdc42 → FRG: "
The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1, a Cdc42-GEF, FRG , and a Rac-GEF, Vav2
"
Cdc42 → Rac-GEF: "
The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1, a Cdc42-GEF, FRG, and a Rac-GEF , Vav2
"
Rac → c-Src: "
The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src , another small G protein, Rap1, a Cdc42-GEF, FRG, and a Rac-GEF, Vav2
"
Rac → Rap1: "
The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1 , a Cdc42-GEF, FRG, and a Rac-GEF, Vav2
"
Rac → Cdc42-GEF: "
The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1, a Cdc42-GEF , FRG, and a Rac-GEF, Vav2
"
Rac → FRG: "
The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1, a Cdc42-GEF, FRG , and a Rac-GEF, Vav2
"
Cdc42 → Rap1: "
The trans-interaction of Necl-5 and nectin-3 also activates Rap1 through C3G, a Rap-GEF, and this activation of Rap1 is required for the activation of Cdc42 and Rac
"
Rac → Rap1: "
The trans-interaction of Necl-5 and nectin-3 also activates Rap1 through C3G, a Rap-GEF, and this activation of Rap1 is required for the activation of Cdc42 and Rac
"
Manually curated Databases
-
NCI Pathway Database Nectin adhesion pathway:
Necl-5(dimer) complex (PVR)
→
nectin-3(dimer)/I-afadin/I-afadin complex (PVRL3-MLLT4)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Nectin adhesion pathway:
Necl-5(dimer) complex (PVR)
→
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer) complex (PVRL3-MLLT4-PVR)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Nectin adhesion pathway:
nectin-3(dimer)/I-afadin/I-afadin complex (PVRL3-MLLT4)
→
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer) complex (PVRL3-MLLT4-PVR)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Nectin adhesion pathway:
VAV2 (VAV2)
→
None
(modification, activates)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Nectin adhesion pathway:
VAV2 (VAV2)
→
RAC1/GDP complex (RAC1)
(modification, activates)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Nectin adhesion pathway:
VAV2 (VAV2)
→
RAC1/GTP complex (RAC1)
(modification, activates)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Nectin adhesion pathway:
VAV2 (VAV2)
→
None
(modification, activates)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Nectin adhesion pathway:
None
→
RAC1/GDP complex (RAC1)
(modification, collaborate)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Nectin adhesion pathway:
None
→
RAC1/GTP complex (RAC1)
(modification, collaborate)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Nectin adhesion pathway:
None
→
None
(modification, collaborate)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Nectin adhesion pathway:
RAC1/GDP complex (RAC1)
→
RAC1/GTP complex (RAC1)
(modification, collaborate)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Nectin adhesion pathway:
RAC1/GDP complex (RAC1)
→
None
(modification, collaborate)
Evidence: mutant phenotype, assay
-
NCI Pathway Database Nectin adhesion pathway:
RAC1/GTP complex (RAC1)
→
None
(modification, collaborate)
Evidence: mutant phenotype, assay
In total, 8 gene pairs are associated to this article in curated databases