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Regulation of mature T lymphocyte proliferation and differentiation by Par-4

By María José Lafuente, Pilar Martin, Isabel Garcia-Cao, María Teresa Diaz-Meco, Manuel Serrano and Jorge Moscat

Abstract

The genetic inactivation of the atypical protein kinase C (aPKC) inhibitor, Par-4, gives rise to increased NF-κB 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-κB 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

Topics: Articles
Publisher: Oxford University Press
Year: 2003
DOI identifier: 10.1093/emboj/cdg460
OAI identifier: oai:pubmedcentral.nih.gov:212727
Provided by: PubMed Central
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