Cutting edge: the metalloproteinase ADAM17/TNF-alpha-converting enzyme regulates proteolytic shedding of the MHC class I-related chain B protein.
J Immunol
; 182(1): 49-53, 2009 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-19109134
ABSTRACT
MHC class I-related chain (MIC) A/B are transmembrane proteins expressed in pathological conditions that are ligands for the activating receptor NKG2D found on cytotoxic lymphocytes. Soluble NKG2D ligands are detected in sera of patients suffering from multiple types of cancer where they are associated with reduced levels of receptor expression and compromised function of NK and CTLs. In this study, we report the identification of a metalloproteinase involved in the cleavage process of MIC; inhibition and knockdown of ADAM17/TACE blocks the shedding of these proteins. Strikingly, the recruitment of both enzyme and substrate to detergent-resistant membrane microdomains is crucial for efficient proteolysis. These findings provide a novel insight into the molecular mechanisms of MIC shedding.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histocompatibility Antigens Class I
/
Membrane Microdomains
/
ADAM Proteins
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Immunol
Year:
2009
Document type:
Article
Affiliation country:
Reino Unido