Protein kinase C (PKC) alpha and PKC theta are the major PKC isotypes involved in TCR down-regulation

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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.
Original languageEnglish
JournalJournal of Immunology
Issue number12
Pages (from-to)7502-10
Number of pages8
Publication statusPublished - 2006

Bibliographical note

Keywords: Amino Acid Motifs; Animals; Antigens, CD3; Cell Line, Tumor; Cells, Cultured; Down-Regulation; Humans; Hybridomas; Isoenzymes; Jurkat Cells; Leucine; Mice; Mice, Knockout; Protein Kinase C; Protein Kinase C-alpha; RNA, Small Interfering; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocyte Subsets

ID: 8544178