caa a22 4500 606234799 CHVBK 20210128101239.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s11010-015-2530-z doi (NATIONALLICENCE)springer-10.1007/s11010-015-2530-z Leukocyte integrin α4β7 associates with heat shock protein 70 [Elektronische Daten] [Yih-Chih Chan, David Greenwood, Yi Yang, Euphemia Leung, Geoffrey Krissansen] The leukocyte integrin cell adhesion molecules α4β7 and αEβ7 mediate the homing and retention of lymphocytes to the gut, and sites of inflammation. Here we have identified heat shock protein 70 (HSP70) as a major protein that associates with the cytoplasmic domain of the integrin β7 subunit. HSPs are molecular chaperones that protect cells from stress but more recently have been reported to also regulate cell adhesion and invasion via modulation of β1, β2, and β3 integrins and integrin-associated signalling molecules. Several HSP70 isoforms including HSP70-3, HSP70-1L, HSP70-8, and HSP70-9 were specifically precipitated from T cells by a bead-conjugated β7 subunit cytoplasmic domain peptide and subsequently identified by high-resolution liquid chromatography-tandem mass spectrometry. In confirmation, the β7 subunit was co-immunoprecipitated from a T cell lysate by an anti-HSP70 antibody. Further, recombinant human HSP70-1a was precipitated by β7 cytoplasmic domain-coupled beads. The HSP70 inhibitor KNK437 decreased the expression of HSP70 without affecting the expression of the β7 integrin. It significantly inhibited α4β7-mediated adhesion of T cells to mucosal addressin cell adhesion molecule 1 (MAdCAM-1), suggesting HSP70 is critical for maintaining β7 integrin signalling function. The functional implications of the association of β7 integrins with the different isoforms of HSP70 warrants further investigation. Springer Science+Business Media New York, 2015 Integrin α4β7 nationallicence Heat shock protein 70 nationallicence Cytoplasmic domain nationallicence Immunoprecipitation nationallicence Mass spectrometry nationallicence Chan Yih-Chih Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand aut Greenwood David Faculty of Science, School of Biological Sciences, University of Auckland, Auckland, New Zealand aut Yang Yi Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand aut Leung Euphemia Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand aut Krissansen Geoffrey Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 263-269 0300-8177 409:1-2<263 2015 409 11010 https://doi.org/10.1007/s11010-015-2530-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 brief-communication jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2530-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chan Yih-Chih Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand aut NATIONALLICENCE 700 1- Greenwood David Faculty of Science, School of Biological Sciences, University of Auckland, Auckland, New Zealand aut NATIONALLICENCE 700 1- Yang Yi Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand aut NATIONALLICENCE 700 1- Leung Euphemia Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand aut NATIONALLICENCE 700 1- Krissansen Geoffrey Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 263-269 0300-8177 409:1-2<263 2015 409 11010