Title | Regulation of mature T lymphocyte proliferation and differentiation by Par-4. |
Publication Type | Journal Article |
Year of Publication | 2003 |
Authors | Lafuente MJosé, Martin P, Garcia-Cao I, Diaz-Meco MTeresa, Serrano M, Moscat J |
Journal | EMBO J |
Volume | 22 |
Issue | 18 |
Pagination | 4689-98 |
Date Published | 2003 Sep 15 |
ISSN | 0261-4189 |
Keywords | Animals, Apoptosis, Apoptosis Regulatory Proteins, Carrier Proteins, Cell Cycle, Cell Differentiation, Cell Division, Gene Deletion, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Lymphocyte Activation, MAP Kinase Signaling System, Mice, Mice, Knockout, Mitogen-Activated Protein Kinases, NFATC Transcription Factors, Protein Kinase C, Receptors, Antigen, T-Cell, T-Lymphocytes |
Abstract | 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. |
DOI | 10.1093/emboj/cdg460 |
Alternate Journal | EMBO J |
PubMed ID | 12970181 |
PubMed Central ID | PMC212727 |
Related Faculty:
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.