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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-6-5
pubmed:abstractText
It is well known that protein kinase C (PKC) plays an important role in regulation of TCR cell surface expression levels. However, eight different PKC isotypes are present in T cells, and to date the particular isotype(s) involved in TCR down-regulation remains to be identified. The aim of this study was to identify the PKC isotype(s) involved in TCR down-regulation and to elucidate the mechanism by which they induce TCR down-regulation. To accomplish this, we studied TCR down-regulation in the human T cell line Jurkat, in primary human T cells, or in the mouse T cell line DO11.10 in which we either overexpressed constitutive active or dominant-negative forms of various PKC isotypes. In addition, we studied TCR down-regulation in PKC knockout mice and by using small interfering RNA-mediated knockdown of specific PKC isotypes. We found that PKCalpha and PKCtheta were the only PKC isotypes able to induce significant TCR down-regulation. Both isotypes mediated TCR down-regulation via the TCR recycling pathway that strictly depends on Ser(126) and the di-leucine-based receptor-sorting motif of the CD3gamma chain. Finally, we found that PKCtheta was mainly implicated in down-regulation of directly engaged TCR, whereas PKCalpha was involved in down-regulation of nonengaged TCR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
176
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7502-10
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16751397-Amino Acid Motifs, pubmed-meshheading:16751397-Animals, pubmed-meshheading:16751397-Antigens, CD3, pubmed-meshheading:16751397-Cell Line, Tumor, pubmed-meshheading:16751397-Cells, Cultured, pubmed-meshheading:16751397-Down-Regulation, pubmed-meshheading:16751397-Humans, pubmed-meshheading:16751397-Hybridomas, pubmed-meshheading:16751397-Isoenzymes, pubmed-meshheading:16751397-Jurkat Cells, pubmed-meshheading:16751397-Leucine, pubmed-meshheading:16751397-Mice, pubmed-meshheading:16751397-Mice, Knockout, pubmed-meshheading:16751397-Protein Kinase C, pubmed-meshheading:16751397-Protein Kinase C-alpha, pubmed-meshheading:16751397-RNA, Small Interfering, pubmed-meshheading:16751397-Receptors, Antigen, T-Cell, pubmed-meshheading:16751397-Signal Transduction, pubmed-meshheading:16751397-T-Lymphocyte Subsets
pubmed:year
2006
pubmed:articleTitle
Protein kinase C (PKC) alpha and PKC theta are the major PKC isotypes involved in TCR down-regulation.
pubmed:affiliation
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't