Cholecystokinin 1 receptor modulates the MEKK1-induced c-Jun trans-activation: structural requirements of the 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.
Laboratoire des Aminoacides, Peptides et Protéines (LAPP), CNRS UMR 5810, UMI et UMII, UFR Pharmacie, 15, avenue Charles Flahault, 34093 Montpellier Cedex 5, France.
Géraldine
G
Ibarz
Catherine
C
Oiry
Eric
E
Carnazzi
Philippe
P
Crespy
Chantal
C
Escrieut
Daniel
D
Fourmy
Jean Claude
JC
Galleyrand
Didier
D
Gagne
Jean
J
Martinez
D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D048728:MAP Kinase Kinase Kinase 1 / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D015533:Transcriptional Activation / Q000502:physiology*
D011949:Receptors, Cholecystokinin; D048031:JNK Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1