| First Author | von Essen M | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 12 | Pages | 7502-10 |
| PubMed ID | 16751397 | Mgi Jnum | J:132355 |
| Mgi Id | MGI:3775728 | Doi | 10.4049/jimmunol.176.12.7502 |
| Citation | von Essen M, et al. (2006) Protein kinase C (PKC) alpha and PKC theta are the major PKC isotypes involved in TCR down-regulation. J Immunol 176(12):7502-10 |
| 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. |
