Article date: April 2006
By: Géraldine Ibarz, Catherine Oiry, Eric Carnazzi, Philippe Crespy, Chantal Escrieut, Daniel Fourmy, Jean Claude Galleyrand, Didier Gagne, Jean Martinez in Volume 147, Issue 8, pages 951-958
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.
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
DOI: 10.1038/sj.bjp.0706690
View this article