The Raf-1/Mitogen-Activated Protein Kinase Kinase-1/Extracellular Signal-Regulated-2 Signaling Pathway as Prerequisite for Interleukin-2 Gene Transcription in Lectin-Stimulated Human Primary T Lymphocytes
| Autor: | Jean Favero, Virginie Lafont, Bruno Rouot |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Transcription
Genetic T-Lymphocytes Mitogen-activated protein kinase kinase Lymphocyte Activation Biochemistry Lectins Humans ASK1 RNA Messenger c-Raf IL-2 receptor Phosphorylation Pharmacology MAP kinase kinase kinase biology Akt/PKB signaling pathway Cyclin-dependent kinase 5 Cyclin-dependent kinase 2 Molecular biology Kinetics Gene Expression Regulation biology.protein Interleukin-2 Plant Lectins Protein Kinases Signal Transduction |
| Zdroj: | Biochemical Pharmacology. 55:319-324 |
| ISSN: | 0006-2952 |
| Popis: | ABSTRACT. It has been shown that stimulation of lymphoid cells causes the activation of the extracellular signal-regulated-2 (ERK-2) which activates nuclear factor of activated T cells (NF-AT), a transcription factor involved in the regulation of interleukin-2 (IL2) gene transcription. ERK-2 is activated via a kinase cascade initiated by activation of the G protein p21Ras followed by phosphorylation and activation of Raf-1 and mitogen-activated protein kinase kinase-1 (MEK-1). Activation of this pathway has been described primarily in human T cell lines; however, using primary T lymphocytes from transgenic mice, a recent study has shown that a blockade of this cascade did not perturb lymphocyte stimulation and proliferation. In the present paper, we studied in human primary T cells the possible involvement of the Raf-1/MEK-1/ERK-2 pathway upon stimulation by jacalin, a mitogenic lectin which specifically stimulates CD4 + lymphocytes. We show here that the mitogen-activated protein (MAP) kinase pathway was stimulated in human purified lymphocytes upon activation with jacalin. Moreover, activation of this pathway appeared to be essential, since its blockade by a specific inhibitor of the MEK-1 kinase abolished IL2 gene transcription; in contrast, in T cells stimulated with phytohemagglutinin M(PHA), another potent T cell mitogenic lectin, blockade of MEK-1 reduced but did not totally inhibit either ERK-2 phosphorylation or IL2 mRNA expression. This shows, as already suggested, that another pathway in addition to the Raf-1/MEK-1/ERK-2 kinase cascade could be triggered in T cell activation. Jacalin stimulation therefore appeared to be a good model for the specific activation of the MAP kinase pathway in human primary T lymphocytes, which would allow the characterisation of drugs specifically targeted to this particular pathway. |
| Databáze: | OpenAIRE |
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