Document Detail

Heparan sulfate modification of the transmembrane receptor CD47 is necessary for inhibition of T cell receptor signaling by thrombospondin-1.
MedLine Citation:
PMID:  21343308     Owner:  NLM     Status:  MEDLINE    
Cell surface proteoglycans on T cells contribute to retroviral infection, binding of chemokines and other proteins, and are necessary for some T cell responses to the matricellular glycoprotein thrombospondin-1. The major cell surface proteoglycans expressed by primary T cells and Jurkat T cells have an apparent M(r) > 200,000 and are modified with chondroitin sulfate and heparan sulfate chains. Thrombospondin-1 bound in a heparin-inhibitable manner to this proteoglycan and to a soluble form released into the medium. Based on mass spectrometry, knockdown, and immunochemical analyses, the proteoglycan contains two major core proteins as follows: amyloid precursor-like protein-2 (APLP2, apparent M(r) 230,000) and CD47 (apparent M(r) > 250,000). CD47 is a known thrombospondin-1 receptor but was not previously reported to be a proteoglycan. This proteoglycan isoform of CD47 is widely expressed on vascular cells. Mutagenesis identified glycosaminoglycan modification of CD47 at Ser(64) and Ser(79). Inhibition of T cell receptor signaling by thrombospondin-1 was lost in CD47-deficient T cells that express the proteoglycan isoform of APLP2, indicating that binding to APLP2 is not sufficient. Inhibition of CD69 induction was restored in CD47-deficient cells by re-expressing CD47 or an S79A mutant but not by the S64A mutant. Therefore, inhibition of T cell receptor signaling by thrombospondin-1 is mediated by CD47 and requires its modification at Ser(64).
Sukhbir Kaur; Svetlana A Kuznetsova; Michael L Pendrak; John M Sipes; Martin J Romeo; Zhuqing Li; Lijuan Zhang; David D Roberts
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2011-02-22
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-25     Completed Date:  2011-07-14     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14991-5002     Citation Subset:  IM    
Laboratory of Pathology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20982, USA.
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MeSH Terms
Amyloid beta-Protein Precursor
Antigens, CD47 / metabolism*
Endothelial Cells
Heparitin Sulfate / metabolism*
Jurkat Cells
Nerve Tissue Proteins
Receptors, Antigen, T-Cell / antagonists & inhibitors*
Serine / metabolism
Signal Transduction*
Thrombospondin 1 / physiology*
Reg. No./Substance:
0/APLP2 protein, human; 0/Amyloid beta-Protein Precursor; 0/Antigens, CD47; 0/CD47 protein, human; 0/Nerve Tissue Proteins; 0/Receptors, Antigen, T-Cell; 0/Thrombospondin 1; 56-45-1/Serine; 9050-30-0/Heparitin Sulfate

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