A pseudosymmetric cell adhesion regulatory domain in the β7 tail of the integrin α4β7 that interacts with focal adhesion kinase and src

Krissansen, Geoffrey W., Singh, Jaison, Kanwar, Rupinder K., Chan, Yih-Chih, Leung, Euphemia, Lehnert, Klaus B., Kanwar, Jagat R. and Yang, Yi 2006, A pseudosymmetric cell adhesion regulatory domain in the β7 tail of the integrin α4β7 that interacts with focal adhesion kinase and src, European journal of immunology, vol. 36, no. 8, pp. 2203-2214.


Title A pseudosymmetric cell adhesion regulatory domain in the β7 tail of the integrin α4β7 that interacts with focal adhesion kinase and src
Author(s) Krissansen, Geoffrey W.
Singh, Jaison
Kanwar, Rupinder K.
Chan, Yih-Chih
Leung, Euphemia
Lehnert, Klaus B.
Kanwar, Jagat R.
Yang, Yi
Journal name European journal of immunology
Volume number 36
Issue number 8
Start page 2203
End page 2214
Publisher Wiley - V C H Verlag GmbH & Co. KGaA
Place of publication Weinheim, Germany
Publication date 2006-08
ISSN 0014-2980
1521-4141
Keyword(s) β7 integrin
cell adhesion regulatory domain
kinases
signal transduction
T cells
Summary The β7 integrins α4β7 and Eβ7 play key roles in forming the gut-associated lymphoid tissue, and contribute to chronic inflammation. The α4β7 integrin-mediated adhesion of activated lymphocytes is largely due to a transient increase in avidity from ligand-induced clustering of α4β7 at the cell-surface. Here, we report that L and D enantiomers of a cell-permeable peptide YDRREY encompassing residues 735-740 of the cytoplasmic tail of the β7 subunit inhibit the adhesion of T cells to β7 integrin ligands. The YDRREY peptide abrogated mucosal addressin cell adhesion molecule-1-induced clustering of α4β7 on the surface of activated T cells. A mutated form of the YDRREY peptide carrying either single or double conservative mutations at Tyr735Phe and Tyr740Phe was unable to inhibit T cell adhesion, suggesting that both tandem tyrosines are critical for activity. The YDRREY peptide was bound and phosphorylated by focal adhesion kinase and src, which may serve to sequester cytoskeletal proteins to the cytoplasmic domain of 4β7. The quasi-palindromic sequence YDRREY within the β7 cytoplasmic tail constitutes a cell adhesion regulatory domain that modulates the interaction of β7-expressing leukocytes with their endothelial and epithelial ligands. Cell-permeable peptidomimetics based on this motif have utility as anti-inflammatory reagents for the treatment of chronic inflammatory disease.
Language eng
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
HERDC collection year 2008
Copyright notice ©2006, WILEY-VCH Verlag GmbH & Co
Persistent URL http://hdl.handle.net/10536/DRO/DU:30019771

Document type: Journal Article
Collection: Institute of Biotechnology
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