Document Detail

Differential regulation and impact of fucosyltransferase VII and core 2 β1,6-N-acetyl-glycosaminyltransferase for generation of E-selectin and P-selectin ligands in murine CD4+ T cells.
MedLine Citation:
PMID:  23039181     Owner:  NLM     Status:  MEDLINE    
Ligands for E-selectin and P-selectin (E-lig and P-lig) are induced on CD4+ T cells upon differentiation into effector T cells. Glycosyltransferases, especially α 1,3-fucosyltransferase VII (FucT-VII) and core 2 β1,6-N-acetyl-glycosaminyltransferase I (C2GlcNAcT-I), are critical for their synthesis. We here analysed the signals that control the expression of E-lig, P-lig and mRNA coding for FucT-VII and C2GlcNAcT-I. In line with previous reports, we found that P-lig expression correlates with the regulation of C2GlcNAcT-I, whereas E-lig expression can occur at low levels of C2GlcNAcT-I mRNA but requires high FucT-VII mRNA expression. Interestingly, the two enzymes are regulated by different signals. Activation-induced C2GlcNAcT-I up-regulation under permissive (T helper type 1) conditions was strongly reduced by cyclosporin A (CsA), suggesting the involvement of T-cell receptor-dependent, calcineurin/NFAT-dependent signals in combination with interleukin-12 (IL-12) -mediated signals in the regulation of C2GlcNAcT-I. In contrast, expression of FucT-VII mRNA was not significantly inhibited by CsA. Interleukin-4 inhibited the expression of FucT-VII but IL-2 and IL-7 were found to support induction of FucT-VII and E-lig. E-selectin, P-selectin and their ligands initially appeared to have rather overlapping functions. These findings however, unravel striking differences in the regulation of E-lig and P-lig expression, dictated by the dominance of FucT-VII and C2GlcNAcT-I, respectively, and their dependency on signals from either promiscuous or homeostatic cytokines (FucT-VII) or a strong T-cell receptor signal in combination with inflammatory cytokines in case of C2GlcNAcT-I.
Micha F Schroeter; Boris A Ratsch; Jeanette Lehmann; Ria Baumgrass; Alf Hamann; Uta Syrbe
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  137     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-21     Completed Date:  2013-02-26     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  294-304     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.
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MeSH Terms
CD4-Positive T-Lymphocytes / metabolism*
Cells, Cultured
Cyclosporine / pharmacology
E-Selectin / metabolism*
Fucosyltransferases / genetics,  physiology*
Gene Expression Regulation, Enzymologic
Interleukin-2 / physiology
Mice, Inbred BALB C
N-Acetylglucosaminyltransferases / genetics,  physiology*
P-Selectin / metabolism*
Receptors, Antigen, T-Cell / physiology
Reg. No./Substance:
0/E-Selectin; 0/Interleukin-2; 0/Ligands; 0/P-Selectin; 0/Receptors, Antigen, T-Cell; 83HN0GTJ6D/Cyclosporine; EC 2.4.1.-/Fucosyltransferases; EC 2.4.1.-/N-Acetylglucosaminyltransferases; EC 2.4.1.-/fucosyltransferase VII, mouse; EC,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase

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