当前位置： SCI文献检索 > EUROPEAN JOURNAL OF IMMUNOLOGY期刊下所有文献 > Palmitoylation of MICA, a ligand for NKG2D, mediates its recruitment to membrane microdomains and promotes its shedding.

Palmitoylation of MICA, a ligand for NKG2D, mediates its recruitment to membrane microdomains and promotes its shedding.

Abstract：

:MICA and MICB (MHC-class-I-related chain A/B) are transmembrane proteins expressed in pathological conditions that are ligands for NKG2D, an activating receptor found on cytotoxic lymphocytes. The recognition on target cells of NKG2D ligands leads to the activation of lysis and cytokine secretion by NK cells and T cells. Besides being expressed at the cell surface, MICA/B can be released as soluble proteins. Soluble NKG2D ligands downmodulate expression of the NKG2D receptor on lymphocytes, leading to a diminished cytotoxic response. Prior studies suggested that recruitment of MICA/B molecules to cholesterol-enriched microdomains was an important factor regulating the proteolytic release of these molecules. We now show that recruitment of MICA to these microdomains depends on palmitoylation of two cysteine residues that allow MICA molecules to reside in the membrane in the same domains as caveolin-1. Compared with WT molecules, nonpalmitoylated mutant MICA molecules were shed to the supernatant with low efficiency; however, both WT and mutant MICA were able to trigger NK cell cytotoxicity. These data suggest that the presence of NKG2D ligands at the plasma membrane is sufficient to activate cytotoxicity and reflect the need of different ligands to exploit different cellular pathways to reach the cell surface upon different stress situations.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Agüera-González S,Gross CC,Fernández-Messina L,Ashiru O,Esteso G,Hang HC,Reyburn HT,Long EO,Valés-Gómez M

doi

10.1002/eji.201141645

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

3667-76

issue

12

eissn

0014-2980

issn

1521-4141

journal_volume

41

pub_type

杂志文章

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