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Cholecystokinin 1 receptor modulates the MEKK1‐induced c‐Jun trans‐activation: structural requirements of the receptor
Author(s) -
Ibarz Géraldine,
Oiry Catherine,
Carnazzi Eric,
Crespy Philippe,
Escrieut Chantal,
Fourmy Daniel,
Galleyrand Jean Claude,
Gagne Didier,
Martinez Jean
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706690
Subject(s) - cholecystokinin b receptor , cholecystokinin , creb , cholecystokinin receptor , receptor , c jun , microbiology and biotechnology , signal transduction , biology , chemistry , transcription factor , biochemistry , gene
In cells overexpressing active MEKK1 to enhance c‐Jun trans‐activation, expression of rat cholecystokinin 1 receptor increased the activity of c‐Jun while in the same experimental conditions overexpression of mouse cholecystokinin 1 receptor repressed it. This differential trans‐activation is specific, since it was not observed for either the other overexpressed kinases (MEK, PKA) or for other transcription factors (ATF2, ELK‐1, CREB). This differential behaviour was also detected in a human colon adenocarcinoma cell‐line naturally producing high levels of endogenous MEKK1. This differential behaviour between the two receptors on the MEKK1‐induced c‐Jun trans‐activation was independent of the activation state of JNK, of the phosphorylation level of c‐Jun and of its ability to bind its specific DNA responsive elements. Two amino acids (Val43 and Phe50 in the mouse cholecystokinin 1 receptor, replaced by Leu43 and Ileu50 in the rat cholecystokinin 1 receptor) localized in the first transmembrane domain were found to play a crucial role in this differential behaviour. MEKK1 probably activates a transcriptional partner of c‐Jun whose activity is maintained or increased in the presence of the rat cholecystokinin 1 receptor but repressed in the presence of the mouse cholecystokinin 1 receptor.British Journal of Pharmacology (2006) 147 , 951–958. doi: 10.1038/sj.bjp.0706690