Allosteric regulation of E-cadherin adhesion

Nitesh Shashikanth, Yuliya I. Petrova, Seongjin Park, Jillian Chekan, Stephanie Maiden, Martha Spano, Taekjip Ha, Barry M. Gumbiner, Deborah E Leckband

Research output: Contribution to journalArticle

Abstract

Cadherins are transmembrane adhesion proteins that maintainintercellular cohesion in all tissues, and their rapid regulationis essential for organized tissue remodeling. Despite some evidence that cadherin adhesion might be allosterically regulated, testing of this has been hindered by the difficulty of quantifyingaltered E-cadherin binding affinity caused by perturbationsoutside the ectodomain binding site. Here, measured kinetics of cadherin-mediated intercellular adhesion demonstratedquantitatively that treatment with activating, anti-Ecadherinantibodies or the dephosphorylation of a cytoplasmic binding partner, p120 ctn , increased the homophilic binding affinity of E-cadherin. Results obtained with Colo 205 cells, which express inactive E-cadherin and do not aggregate, demonstratedthat four treatments, which induced Colo 205 aggregationand p120 ctn dephosphorylation, triggered quantitatively similar increases in E-cadherin affinity. Several processes can alter cell aggregation, but these results directly demonstratedthe allosteric regulation of cell surface E-cadherin by p120 ctn dephosphorylation.

Original languageEnglish (US)
Pages (from-to)21749-21761
Number of pages13
JournalJournal of Biological Chemistry
Volume290
Issue number35
DOIs
StatePublished - Aug 28 2015

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Allosteric Regulation
Cadherins
Adhesion
Tissue
Cell Aggregation
Agglomeration
Binding Sites
Cells
Kinetics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Shashikanth, N., Petrova, Y. I., Park, S., Chekan, J., Maiden, S., Spano, M., ... Leckband, D. E. (2015). Allosteric regulation of E-cadherin adhesion. Journal of Biological Chemistry, 290(35), 21749-21761. https://doi.org/10.1074/jbc.M115.657098

Allosteric regulation of E-cadherin adhesion. / Shashikanth, Nitesh; Petrova, Yuliya I.; Park, Seongjin; Chekan, Jillian; Maiden, Stephanie; Spano, Martha; Ha, Taekjip; Gumbiner, Barry M.; Leckband, Deborah E.

In: Journal of Biological Chemistry, Vol. 290, No. 35, 28.08.2015, p. 21749-21761.

Research output: Contribution to journalArticle

Shashikanth, N, Petrova, YI, Park, S, Chekan, J, Maiden, S, Spano, M, Ha, T, Gumbiner, BM & Leckband, DE 2015, 'Allosteric regulation of E-cadherin adhesion', Journal of Biological Chemistry, vol. 290, no. 35, pp. 21749-21761. https://doi.org/10.1074/jbc.M115.657098
Shashikanth N, Petrova YI, Park S, Chekan J, Maiden S, Spano M et al. Allosteric regulation of E-cadherin adhesion. Journal of Biological Chemistry. 2015 Aug 28;290(35):21749-21761. https://doi.org/10.1074/jbc.M115.657098
Shashikanth, Nitesh ; Petrova, Yuliya I. ; Park, Seongjin ; Chekan, Jillian ; Maiden, Stephanie ; Spano, Martha ; Ha, Taekjip ; Gumbiner, Barry M. ; Leckband, Deborah E. / Allosteric regulation of E-cadherin adhesion. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 35. pp. 21749-21761.
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