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-agonis t isoproterenol. Sequence comparisons between mice and hamster proline -rich protein genes identified conserved regions upstream from the tra nscription start site. Reporter plasmids containing these 5'-flanking sequences from a mouse proline-rich protein gene, MP2, were constructe d and tested for transcriptional regulation by cAMP. Transient transfe ction 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 o f 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 analysi s, Nuclear proteins isolated from mouse parotid glands protected the c onsensus AP-1 binding site 5'-TGAGTCA-3' (-592 to -586). The nuclear p roteins interacting at this site were increased about sixfold in gland s isolated from isoproterenol-treated mice when compared with glands f rom untreated mice. These results suggest that induction of AP-1 trans cription factors in the parotid gland control the upregulation of some mouse salivary proline-rich proteins. (C) 1997 Academic Press.