Cathepsin X cleavage of the ß2 integrin regulates talin-binding and LFA-1 affinity in T cells
Jevnikar, Zala (Author), Obermajer, Nataša (Author), Doljak, Bojan (Author), Turk, Samo (Author), Gobec, Stanislav (Author), Švajger, Urban (Author), Hailfinger, Stephan (Author), Thome, Margot (Author), Kos, Janko (Author)

URLURL - Presentation file, Visit http://www.jleukbio.org/content/early/2011/03/31/jlb.1110622.abstract This link opens in a new window

T cell migration, essential for immune surveillance and response, is mediated by the integrin LFA-1. CatX, a cysteine carboxypeptidase, is involved in the regulation of T cell migration by interaction with LFA-1. We show that sequential cleavage of C-terminal amino acids from the ?2 cytoplasmic tail of LFA-1, by CatX, enhances binding of the adaptor protein talin to LFA-1 and triggers formation of the latter's high-affinity form. As shown by SPR analysis of peptides constituting the truncated ?2 tail, the cleavage of three C-terminal amino acids by CatX resulted in a 1.6-fold increase of talin binding. Removal of one more amino acid resulted in a 2.5-fold increase over the intact tail. CatX cleavage increased talin-binding affinity to the MD but not the MP talin-binding site on the ?2 tail. This was shown by molecular modeling of the ?2 tail/talin F3 complex to be a result of conformational changes affecting primarily the distal-binding site. Analysis of LFA-1 by conformation-specific mAb showed that CatX modulates LFA-1 affinity, promoting formation of high-affinity from intermediate-affinity LFA-1 but not the initial activation of LFA-1 from a bent to extended form. CatX post-translational modifications may thus represent a mechanism of LFA-1 fine-tuning that enables the trafficking of T cells

Keywords:katepsin X, T celice, LFA-1, ß2 integrin
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Number of pages:str. 99-109
Numbering:Vol. 90, no. 1
ISSN on article:0741-5400
DOI:10.1189/jlb.1110622 Link is opened in a new window
COBISS.SI-ID:2988913 Link is opened in a new window
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Record is a part of a journal

Title:Journal of leukocyte biology
Shortened title:J. leukoc. biol.
COBISS.SI-ID:3225615 This link opens in a new window

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