| First Author | Lafuente MJ | Year | 2003 |
| Journal | EMBO J | Volume | 22 |
| Issue | 18 | Pages | 4689-98 |
| PubMed ID | 12970181 | Mgi Jnum | J:85495 |
| Mgi Id | MGI:2675524 | Doi | 10.1093/emboj/cdg460 |
| Citation | Lafuente MJ, et al. (2003) Regulation of mature T lymphocyte proliferation and differentiation by Par-4. EMBO J 22(18):4689-98 |
| abstractText | The genetic inactivation of the atypical protein kinase C (aPKC) inhibitor, Par-4, gives rise to increased NF-kappaB activation and decreased stimulation of JNK in embryo fibroblasts. Here we have characterized the immunological phenotype of the Par-4(-/-) mice and found that the loss of this gene leads to an increased proliferative response of peripheral T cells when challenged through the TCR. This is accompanied by a higher increase in cell cycle entry and inhibition of apoptosis, with enhanced IL-2 secretion but normal CD25 synthesis. Interestingly, the TCR-triggered activation of NF-kappaB was augmented and that of JNK was severely abrogated. Consistent with previous data from knock outs of different JNKs, NFATc1 activation and IL-4 secretion were augmented in the Par-4-deficient CD4+ T cells, suggesting that the loss of Par-4 drives T-cell differentiation towards a Th2 response. This is compelling evidence that Par-4 is a novel modulator of the immune response through its ability to impact aPKC activity, which translates into lower JNK signaling. |
