Molecular cloning and functional characterization of the human platelet-derived growth factor alpha receptor gene promoter.
Expression of the platelet-derived growth factor alpha receptor (PDGF alpha R) is strictly regulated during mammalian development and tumorigenesis. The molecular mechanisms involved in the specific regulation of PDGF alpha R expression are unknown, but transcriptional regulation of the PDGF alpha R gene is most likely to be involved. This study describes the molecular cloning of the non-coding exon 1 and approximately 2 kb of 5' flanking region of the human PDGF alpha R gene. This 5' flanking region is a functional promoter of the PDGF alpha R gene as concluded from its capacity to drive luciferase reporter gene expression in an orientation dependent way. Analysis of 5' promoter deletion mutants revealed that the region from -441 to +118, relative to the transcription initiation site, is sufficient to establish high level promoter activity. In addition, the morphogen retinoic acid, alone or in combination with dibutyryl cAMP, gives a 22-fold induction of PDGF alpha R gene promoter activity in human teratocarcinoma cells. This effect is mediated through specific transcription factor binding within the -52/+118 region of the PDGF alpha R gene.
Afink
G B
GB
Department of Cell Biology, University of Nijmegen, The Netherlands.
Nistér
M
M
Stassen
B H
BH
Joosten
P H
PH
Rademakers
P J
PJ
Bongcam-Rudloff
E
E
Van Zoelen
E J
EJ
Mosselman
S
S
D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics*; D016385:TATA Box; D013806:Theophylline / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D014212:Tretinoin; D003994:Bucladesine; D013806:Theophylline; D017479:Receptors, Platelet-Derived Growth Factor