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Cell-cell adhesion-mediated tyrosine phosphorylation of nectin-2δ, an immunoglobulin-like cell adhesion molecule at adherens junctions

Abstract

We have recently found a novel functional unit of cell-cell adhesion at cadherin-based adherens junctions, consisting of at least nectin, an immunoglobulin-like cell adhesion molecule, and afadin, an actin filament-binding protein which connects nectin to the actin cytoskeleton. Among the members of the nectin family, we have found here that nectin-2δ is tyrosine-phosphorylated in response to cell-cell adhesion. Expression of E-cadherin induced tyrosine phosphorylation of nectin-2δ, while disruption of cell-cell adhesion by an anti-E-cadherin antibody reduced the tyrosine phosphorylation of nectin-2δ. An inhibitor specific for Src family kinase or expression of Csk reduced tyrosine phosphorylation of nectin-2δ. In addition, Src kinase tyrosine phosphorylates the recombinant cytoplasmic region of nectin-2δ in vitro. The major tyrosine phosphorylation site of nectin-2δ was Tyr505 in the cytoplasmic region, because the mutant nectin-2δ, of which Tyr505 was replaced by Phe, showed a loss of tyrosine phosphorylation in vivo and in vitro. These results, together with our recent observations, indicate that the cadherin-catenin system and the nectin-afadin system are closely connected to each other. The cadherin-mediated cell-cell adhesion system may link to the activation of a Src family kinase, that is, at least in part, responsible for the tyrosine phosphorylation of the cytoplasmic region of nectin-2δ.

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Acknowledgements

We are grateful to Drs Sh Tsukita and A Nagafuchi (Kyoto University, Kyoto, Japan) for L and EL cells. We also thank Drs A Nomoto and J Aoki (Tokyo University, Tokyo, Japan) for the anti-nectin-2 mAb.

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Kikyo, M., Matozaki, T., Kodama, A. et al. Cell-cell adhesion-mediated tyrosine phosphorylation of nectin-2δ, an immunoglobulin-like cell adhesion molecule at adherens junctions. Oncogene 19, 4022–4028 (2000). https://doi.org/10.1038/sj.onc.1203744

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