T cell activation leads via multiple intracellular signaling pathways to rapid induction of @entity1199 ( @entity1199 ) expression, which can be mimicked by costimulation with @entity864 ( @entity865 ) and @entity1360 . We have identified a distal @entity1199 enhancer regulated by the Raf-MEK- @entity3963 signaling pathway, which can be induced by @entity865 / @entity1360 treatment. It contains a dyad symmetry element (DSE) controlled by the Ets-like transcription factor GA-binding protein (GABP), a target of activated @entity3963 . @entity865 / @entity1360 treatment of T cells stimulates both mitogen-activated @entity3963 , as well as the stress-activated mitogen-activated protein kinase family members @entity4675 / @entity5183 and @entity1435 . In this study, we investigated the contribution of the stress-activated pathways to the induction of the distal @entity1199 enhancer. We show that @entity4675 - but not @entity1435 -activating pathways regulate the DSE activity. Furthermore, the @entity4675 / @entity5183 signaling pathway cooperates with the Raf-MEK- @entity3963 cascade in @entity865 / @entity1360 -induced DSE activity. In T cells, overexpression of @entity21576 / @entity21576 , an activator of @entity10886 , strongly induces DSE-dependent transcription and dominant negative kinases of SEK and @entity5183 impair @entity865 / @entity1360 -induced DSE activity. Blocking both @entity3963 and @entity10886 pathways abolishes the DSE induction. The inducibility of the DSE is strongly dependent on the Ets-core motifs, which are bound by GABP. Both subunits of GABP are phosphorylated upon @entity4675 activation in vivo and three different isoforms of @entity10886 , but not @entity1435 , in vitro. Our data suggest that GABP is targeted by signaling events from both @entity3963 and @entity4675 / @entity5183 pathways. GABP therefore is a candidate for signal integration and regulation of @entity1199 transcription in T lymphocytes.

The GABP-responsive element of the @entity1199 enhancer is regulated by XXXX / @entity5183 -activating pathways in T lymphocytes.

@entity21576 :: ('4296', 'Gene') :: ['MLK3', 'SPRK'] @entity3963 :: ('5594', 'Gene') :: ['ERK'] @entity5183 :: ('5601', 'Gene') :: ['SAPK'] @entity1360 :: ('MESH:D015759', 'Chemical') :: ['ionomycin'] @entity865 :: ('CHEBI:61432', 'Chemical') :: ['TPA'] @entity4675 :: ('5599', 'Gene') :: ['JNK'] @entity1435 :: ('1432', 'Gene') :: ['p38'] @entity1199 :: ('3558', 'Gene') :: ['interleukin-2', 'IL-2'] @entity864 :: ('MESH:C554292|MESH:D013755', 'Chemical') :: ['12-O-tetradecanoylphorbol-13-acetate'] @entity10886 :: ('5599;5601', 'Gene') :: ['JNK/SAPK']
@entity4675 :: (5599,Gene) :: ['JNK']
