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 |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/CD3 antigen, gamma chain,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Leucine,
http://linkedlifedata.com/resource/pubmed/chemical/Prkca protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Prkcq protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell
|
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
|