The Ca2+/calmodulin-dependent kinase type IV is involved in the CD5- mediated signaling pathway in human T lymphocytes

Sonja I. Gringhuis, Lou F.M.H. De Leij, Gary A. Wayman, Hiroshi Tokumitsu, Edo Vellenga

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40 Citations (Scopus)


The CD5 receptor on T lymphocytes is involved in T cell activation and T-B cell interactions. In the present study, we have characterized the signaling pathways induced by anti-CD5 stimulation in human T lymphocytes. In T lymphocytes, anti-CD5 co-stimulation enhances the phytohemagglutinin/anti- CD28-induced interleukin-2 (IL-2) mRNA accumulation 1.6-fold and IL-2 protein secretion 2.2-fold, whereby the up-regulation is mediated at both the transcriptional and post-transcriptional level. The CD5 signaling pathway up- regulates the IL-2 genes expression by increasing the DNA binding and transactivation activity of activator protein 1 but affects none of the other transcription factors like nuclear factor of activated T cells, nuclear factor κB, Oct, and CD28-responsive complex/nuclear factor of mitogen- activated T cells involved in the regulation of the IL-2 promoter activity. The CD5-induced increase of the activator protein 1 activity is mediated through the activation of calcium/calmodulin-dependent (CaM) kinase type IV, and is independent of the activation of mitogen-activated protein kinases Jun N-terminal kinase, extra-cellular signal-regulated kinase, and p38/Mpk2, and calcium/calmodulin-dependent kinase type II. The expression of a dominant negative mutant of CaM kinase IV in T lymphocytes transfected with an IL-2 promoters-driven reporter construct completely abrogates the response to CD5 stimulation, indicating that CaM kinase IV is essential to the CD5 signaling pathway. In addition, it is demonstrated that calcium/calmodulin-dependent kinase type IV is also involved in the stabilization of the IL-2 transcripts, which is observed after co-stimulation of phytohemagglutinin/anti-CD28 activated T lymphocytes with anti-CD5.

Original languageEnglish
Pages (from-to)31809-31820
Number of pages12
JournalJournal of Biological Chemistry
Issue number50
Publication statusPublished - Dec 12 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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