Cyclic AMP regulation of mouse proline-rich protein gene expression: isoproterenol induction of AP-1 transcription factors in parotid glands.
Proline-rich protein mRNAs are increased dramatically in the salivary glands of rats, mice, and hamsters upon treatment with the beta-agonist isoproterenol. Sequence comparisons between mice and hamster proline-rich protein genes identified conserved regions upstream from the transcription start site. Reporter plasmids containing these 5'-flanking sequences from a mouse proline-rich protein gene, MP2, were constructed and tested for transcriptional regulation by cAMP. Transient transfection experiments in mouse L-M cells showed that the upstream region -702 to -322 bp relative to the transcription start site is sufficient to confer cAMP induction on a heterologous promoter. Multiple copies of the AP-1 sequence elements within this region (-625 to -551) mediate the cAMP transcriptional response of reporter gene expression in L-M cells. L-M cell nuclear proteins and purified human c-jun protein bind to these upstream elements as determined by DNase I footprint analysis. Nuclear proteins isolated from mouse parotid glands protected the consensus AP-1 binding site 5'-TGAGTCA-3' (-592 to -586). The nuclear proteins interacting at this site were increased about sixfold in glands isolated from isoproterenol-treated mice when compared with glands from untreated mice. These results suggest that induction of AP-1 transcription factors in the parotid gland control the upregulation of some mouse salivary proline-rich proteins.
Zhou
J
J
Section of Molecular and Cellular Biology, University of California, Davis 95616, USA.
Wright
P S
PS
Wong
E
E
Jessen
K
K
Morand
J N
JN
Carlson
D M
DM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D016384:Consensus Sequence; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015342:DNA Probes / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000235:genetics*; D055232:Proline-Rich Protein Domains; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*
D000318:Adrenergic beta-Agonists; D015342:DNA Probes; D010455:Peptides; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D004247:DNA; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase; D007545:Isoproterenol