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Molecular and Cellular Biology, January 2002, p. 23-29, Vol. 22, No. 1
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.1.23-29.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Defective Signaling in a Subpopulation of CD4+ T Cells in the Absence of Ca2+/Calmodulin-Dependent Protein Kinase IV

Kristin A. Anderson and Anthony R. Means*

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 22710

Received 16 May 2001/ Returned for modification 3 July 2001/ Accepted 18 September 2001

Ca2+/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.

* Corresponding author. Mailing address: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 22710. Phone: (919) 681-6209. Fax: (919) 681-7767. E-mail: means001{at}mc.duke.edu.

Molecular and Cellular Biology, January 2002, p. 23-29, Vol. 22, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.1.23-29.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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