Overexpression of mitogen-activated protein kinase kinase kinase reversed cAMP inhibiton of NF-κB in T cells
Journal
European Journal of Immunology
Journal Volume
27
Journal Issue
1
Pages
222-226
Date Issued
1997
Author(s)
Abstract
cAMP inhibits T cell activation by acting as an antagonist for selective kinases and transcriptional factors. We have recently demonstrated that cAMP inhibited c-Jun N-terminal kinase (JNK) but left the mitogen-activated protein (MAP) kinase cascade almost unaffected in T lymphocytes. In accordance with recent reports, we also observed a selective suppression of nuclear factor NF-κB activation by cAMP. The possible link between the JNK cascade and NF-κB activation was demonstrated by the fact that the active form of MAP kinase kinase kinase (ΔMEKK), a constitutive activator of JNK, induced NF-κB but not AP-1, Oct, and NF-AT in T cells. In contrast, the induction of MAP kinase kinase (MEK)-MAP kinase did not stimulate NF-κB activity. The specific activation of NF-κB by a single MEKK-JNK cascade was thus unusual, given that the activation of other transcriptional elements in T cells requires at least two signal pathways. This was further confirmed by the fact that cAMP inhibition of NF-κB activation was reversed by overexpression of ΔMEKK.
Type
journal article