IngentaConnect Common signaling pathway is used by the trans-interaction of Necl...

Authors: Sato, Tatsuhiro¹; Irie, Kenji; Okamoto, Ryoko¹; Ooshio, Takako¹; Fujita, Naoyuki¹; Takai, Yoshimi

Source: Cancer Science, Volume 96, Number 9, September 2005 , pp. 578-589(12)

Abstract:

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. (Cancer Sci 2005; 96: 578 –589)

Document Type: Research article

DOI: 10.1111/j.1349-7006.2005.00087.x

Affiliations: 1: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine, Faculty of Medicine, Suita 565–0871, Japan

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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