Affiliation:
1. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 22710
Abstract
ABSTRACT
Ca
2+
/calmodulin-dependent protein kinase IV-deficient (CaMKIV
−/−
) mice have been used to investigate the role of this enzyme in CD4
+
T cells. We identify a functional defect in a subpopulation of CD4
+
T cells, characterized by a cell surface marker profile usually found on memory phenotype CD4
+
T cells. Upon T-cell receptor engagement, the mutant cells produce diminished levels of interleukin-2 (IL-2), IL-4, and gamma interferon protein and mRNA. The defect is secondary to an inability to phosphorylate CREB and to induce CREB-dependent immediate-early genes, including c-
jun
,
fosB
,
fra2
, and
junB
, which are required for cytokine gene induction. In contrast, stimulated naive CD4
+
T cells from CaMKIV
−/−
mice show normal CREB phosphorylation, induction of immediate-early genes, and cytokine production. Thus, in addition to defining an important signaling role for CaMKIV in a subpopulation of T cells, we identify differential signaling requirements for cytokine production between naive T cells and T cells that express cell surface markers characteristic of the memory phenotype.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
45 articles.
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