Gene interactions and pathways from curated databases and text-mining
Cancer Sci 2005, PMID: 16128743

Common signaling pathway is used by the trans-interaction of Necl-5/Tage4/PVR/CD155 and nectin, and of nectin and nectin during the formation of cell-cell adhesion.

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