Identification of a binding site for integrin alphaEbeta7 in the N-terminal domain of E-cadherin.

The Journal of Biological Chemistry
P KareclaP J Kilshaw

Abstract

The integrin alphaEbeta7, which is predominantly expressed on mucosal T lymphocytes, has recently been shown to recognize the cell adhesion molecule, E-cadherin, on epithelial cells. We have carried out mutations on E-cadherin, involving domain deletions as well as substitutions of specific amino acids, in order to identify the sites recognized by the integrin. Binding of alphaEbeta7 required the presence of the first two N-terminal domains of E-cadherin. Deletion of extracellular domains 3 and 4 or truncation of the cytoplasmic domain of E-cadherin had no consequence on integrin binding. Substitution of a glutamic acid in the BC loop of the Ig structure of the fist, N-terminal, domain of E-cadherin abrogated binding of alphaEbeta7. This mutation did not appear to affect the conformation of the domain nor the pattern of expression of E-cadherin on the cell surface. Synthetic peptides encompassing the first domain of E-cadherin had very little inhibitory effect on the interaction with alphaEbeta7. Our results highlight structural dissimilarities between recognition of E-cadherin by alphaEbeta7 and recognition of other members of the IgSF by integrins and show that the heterophilic (integrin binding) and homophilic sites in the N...Continue Reading

References

Jan 1, 1992·Annual Review of Cell Biology·B Geiger, O Ayalon
Dec 1, 1990·Mechanisms of Development·M OzawaR Kemler
Jan 1, 1991·Immunologic Research·S SarnackiN Cerf-Bensussan
Apr 1, 1991·The Journal of Cell Biology·U H FrixenW Birchmeier
Oct 1, 1990·European Journal of Immunology·P J Kilshaw, S J Murant
Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M OzawaR Kemler
Jun 1, 1988·Immunology Letters·P J Kilshaw, K C Baker
Jan 1, 1987·Methods in Enzymology·T A KunkelR A Zakour
Sep 1, 1987·European Journal of Immunology·N Cerf-BensussanC Griscelli
Mar 23, 1995·Nature·L ShapiroW A Hendrickson
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·P Cowin
Jul 1, 1993·European Journal of Immunology·K Roberts, P J Kilshaw
Feb 1, 1993·European Journal of Immunology·M HauryM D Cooper

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Citations

Oct 24, 2002·Matrix Biology : Journal of the International Society for Matrix Biology·John D WhittardMartin J Humphries
Feb 22, 2002·European Journal of Biochemistry·Alexis AquilinaDanny Tuckwell
May 3, 2000·The Journal of Experimental Medicine·K S TaraszkaM B Brenner
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Matteo BonazziPascale Cossart
Mar 1, 2000·Molecular Pathology : MP·P J Kilshaw
Jan 19, 1999·Annual Review of Cell and Developmental Biology·S Dramsi, P Cossart
Aug 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·M LecuitP Cossart
Feb 14, 1998·The Journal of Cell Biology·J M HigginsM B Brenner
Aug 4, 2004·Cellular and Molecular Life Sciences : CMLS·A W KochW Shan
Sep 21, 2001·The Journal of Investigative Dermatology·K PaulsM P Schön
Jan 1, 1997·Annual Review of Biochemistry·C Chothia, E Y Jones
Apr 28, 2004·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jane M GoodingMitsuhiko Ikura
Apr 28, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Eimear DunneDermot Kenny
Feb 5, 2009·Cellular Microbiology·Matteo BonazziPascale Cossart
May 5, 2010·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Karolina A RygielJohn A Kirby
Apr 30, 2003·Japanese Journal of Cancer Research : Gann·Motoi TakeuchiChie Furihata
Jan 5, 1999·The Journal of Biological Chemistry·Q ZenM J Telen
Nov 7, 1998·The Journal of Biological Chemistry·T L BachJ Martinez
Jun 6, 2000·The Journal of Biological Chemistry·J M HigginsM B Brenner
Jul 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kiyono ShiraishiTsutomu Takeuchi
Apr 26, 2020·Cells·Michele Sommariva, Nicoletta Gagliano
Sep 2, 1998·The American Journal of Physiology·S K ShawJ L Madara
May 9, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S M MartinR G Lorenz
Jun 24, 1997·Biochemistry·A W KochJ Engel

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