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PMID:12970181
| Citation |
Lafuente, MJ, Martin, P, Garcia-Cao, I, Diaz-Meco, MT, Serrano, M and Moscat, J (2003) Regulation of mature T lymphocyte proliferation and differentiation by Par-4. EMBO J. 22:4689-98 |
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| 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. |
| Links |
PubMed PMC212727 Online version:10.1093/emboj/cdg460 |
| Keywords |
Animals; Apoptosis; Apoptosis Regulatory Proteins; Carrier Proteins/genetics; Carrier Proteins/physiology; Cell Cycle; Cell Differentiation; Cell Division/genetics; Gene Deletion; Intracellular Signaling Peptides and Proteins; JNK Mitogen-Activated Protein Kinases; Lymphocyte Activation/genetics; Lymphocyte Activation/physiology; MAP Kinase Signaling System; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases/metabolism; NFATC Transcription Factors; Protein Kinase C/deficiency; Protein Kinase C/genetics; Protein Kinase C/physiology; Receptors, Antigen, T-Cell/physiology; T-Lymphocytes/cytology; T-Lymphocytes/immunology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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