Serum induction of the collagen X promoter requires the Raf/MEK/ERK and p38 pathways.
The collagen X gene is expressed exclusively by differentiated, hypertrophic chondrocytes. The mechanisms controlling collagen X expression remain largely unknown. Here we show that collagen X promoter activity can be induced by serum stimulation of chondrogenic MCT cells. The serum response is conferred by a 462 nucleotide promoter fragment. Both the c-Raf/MEK/ERK and p38 MAP kinase pathways are required for this effect, whereas phosphatidylinositol-3-kinase and protein kinase A repress promoter activation. These data are the first to demonstrate serum inducibility of the collagen X promoter and to identify signal transduction pathways involved.
Beier
F
F
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, 3330 Hospital Drive NW, T2N 4N1, Canada.
LuValle
P
P
D000730:Androstadienes / Q000494:pharmacology; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003094:Collagen / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases
D000730:Androstadienes; D001798:Blood Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003094:Collagen; D017868:Cyclic AMP-Dependent Protein Kinases; D005419:Flavonoids; D007093:Imidazoles; D007546:Isoquinolines; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D019908:Proto-Oncogene Proteins c-raf; D011725:Pyridines; D013449:Sulfonamides; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases; C482125:MAP2K1 protein, human; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one