RT Journal Article SR Electronic T1 CholecystokininB Receptor from Human Jurkat Lymphoblastic T Cells Is Involved in Activator Protein-1-Responsive Gene Activation JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 292 OP 299 DO 10.1124/mol.52.2.292 VO 52 IS 2 A1 Catherine Oiry A1 Didier Gagne A1 Éric Cottin A1 Nicole Bernad A1 Jean-Claude Galleyrand A1 Gilbert Bergé A1 Marie-Francoise Lignon A1 Patrick Eldin A1 Martine Le Cunff A1 Jean Léger A1 Pascal Clerc A1 Daniel Fourmy A1 Jean Martinez YR 1997 UL http://molpharm.aspetjournals.org/content/52/2/292.abstract AB The aim of this study was to analyze the role of cholecystokinin (CCKB) receptor in human lymphoblastic Jurkat T cells. We investigated the trophic effect resulting from activation of such a receptor by using the reporter gene strategy. For this purpose, we transiently transfected Jurkat T cells with the reporter plasmid p[(TRE)3-tk-Luc] and found that CCK-8 was able to dose-dependently induce luciferase expression related to activator protein-1 (AP-1) activation with a maximal response identical to that obtained with compounds known to activate AP-1 complex (quantitatively, the same level of induction was obtained with 1 nm12-O-tetradecanoylphorbol-13-acetate, 100 μm diacylglycerol, or 4 nm epidermal growth factor). The involvement of the CCKB receptor in such a stimulation was demonstrated by the inhibiting effect of the selective CCKB receptor antagonist PD-135,158. This effect was confirmed in COS-7 cells transfected with the cDNA of CCKBreceptor cloned from Jurkat T cells. To better understand the AP-1-dependent luciferase expression in Jurkat T cells, we tested two specific inhibitors of serine/threonine phosphatases-1 and -2A: okadaic acid and calyculin A. These compounds strongly increased the phorbol-12-myristate-13-acetate response, whereas we have not observed a contribution of phosphatase inhibitors on a CCK-8-induced luciferase activity. To confirm that CCKB receptors are involved in AP-1 response, we investigated the CCK-8 effect on interleukin-2 expression, a natural endogenous gene regulated by several factors, including AP-1. In Jurkat T cells activated by phorbol-12-myristate-13-acetate and phytohemagglutinin, CCK-8 induced IL-2 expression. This induction was abolished by PD-135,158. Our results indicate that CCK-8 exerts a trophic effect in Jurkat T cells through stimulation of CCKB receptors by modulation of expression of AP-1-regulated genes.