Defective signaling in a subpopulation of CD4(+) T cells in the absence of Ca(2+)/calmodulin-dependent protein kinase IV

Mol Cell Biol. 2002 Jan;22(1):23-9. doi: 10.1128/MCB.22.1.23-29.2002.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cytokines / metabolism*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Genes, Immediate-Early / genetics
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Phenotype
  • Ribosomal Protein S6 Kinases / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism
  • Transcriptional Activation

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Cytokines
  • DNA-Binding Proteins
  • Interleukin-2
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Transcription Factors
  • Interleukin-4
  • Interferon-gamma
  • Ribosomal Protein S6 Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Camk4 protein, mouse