Neurotensin type 1 receptor-mediated activation of krox24, c-fos and Elk-1: preventing effect of the neurotensin antagonists SR 48692 and SR 142948.
Stimulation of neurotensin (NT) type 1 receptors (NT1-R) in transfected CHO cells is followed by the activation of mitogen-activated protein kinases and the expression of the early response gene krox24. By making point mutations and internal deletions in the krox24 promoter, we show that proximal serum responsive elements (SRE) are involved in transcriptional activation by NT. In addition, we show that the related early response gene c-fos and the Ets protein Elk-1 are also induced by NT. The involvement of NT1-R in NT-mediated activation of krox24, c-fos and Elk-1 was demonstrated by the preventing effect of the specific antagonists SR 48692 and SR 142948. Finally, we show that the activation of krox24 and Elk-1 on the one hand, and that of c-fos on the other hand, result from independent transduction pathways since the former are pertussis toxin-sensitive whereas the latter is insensitive to pertussis toxin.
Portier
M
M
Sanofi Recherche, Montpellier, France. marielle.portier@tls1.elfsanofi.fr
Combes
T
T
Gully
D
D
Maffrand
J P
JP
Casellas
P
P
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D007093:Imidazoles / Q000494:pharmacology; D009496:Neurotensin / Q000037:antagonists & inhibitors*; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D018028:Receptors, Neurotensin / Q000378:metabolism*; D017384:Sequence Deletion; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; D007093:Imidazoles; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C104418:SR 142948A; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; C114036:neurotensin type 1 receptor; C079087:SR 48692; D009496:Neurotensin; D000218:Adamantane