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

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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
Volume272
Issue number50
DOIs
Publication statusPublished - Dec 12 1997
Externally publishedYes

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinases
T-cells
Calmodulin
Interleukin-2
Phosphotransferases
T-Lymphocytes
NFATC Transcription Factors
Transcription Factor AP-1
Phytohemagglutinins
Calcium
Chemical activation
Up-Regulation
TCF Transcription Factors
Mitogen-Activated Protein Kinases
Mitogens
Cell Communication
Transcriptional Activation
Gene expression
B-Lymphocytes
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry

Cite this

The Ca2+/calmodulin-dependent kinase type IV is involved in the CD5- mediated signaling pathway in human T lymphocytes. / Gringhuis, Sonja I.; De Leij, Lou F M H; Wayman, Gary A.; Tokumitsu, Hiroshi; Vellenga, Edo.

In: Journal of Biological Chemistry, Vol. 272, No. 50, 12.12.1997, p. 31809-31820.

Research output: Contribution to journalArticle

Gringhuis, Sonja I. ; De Leij, Lou F M H ; Wayman, Gary A. ; Tokumitsu, Hiroshi ; Vellenga, Edo. / The Ca2+/calmodulin-dependent kinase type IV is involved in the CD5- mediated signaling pathway in human T lymphocytes. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 50. pp. 31809-31820.
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