Article
- The EMBO Journal (2003) 22, 4689 - 4698
- doi:10.1093/emboj/cdg460
Subject Categories:
Regulation of mature T lymphocyte proliferation and differentiation by Par-4
María José Lafuente1,3, Pilar Martin1,3, Isabel Garcia-Cao2,3, María Teresa Diaz-Meco1, Manuel Serrano2 and Jorge Moscat1
- Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Canto Blanco, 28049 Madrid, Spain
- Departamento de Immunología y Oncología, Centro Nacional de Biotecnología, Canto Blanco, 28049 Madrid, Spain
- M.J.Lafuente, P.Martin and I.Garcia-Cao contributed equally to this work
Correspondence to:
Jorge Moscat, E-mail: jmoscat@cbm.uam.es
Received 27 May 2003; Accepted 24 July 2003; Revised 23 July 2003
Abstract
The genetic inactivation of the atypical protein kinase C (aPKC) inhibitor, Par-4, gives rise to increased NF-
B 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-B 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.
Keywords:
- atypical PKCs,
- B lymphocytes,
- NF-B,
- Par-4,
- T lymphocytes
