Protein kinase C alpha, epsilon and AP-1 mediate prolactin regulation of mitochondrial aspartate aminotransferase expression in the rat lateral prostate.
Citrate accumulation and secretion are physiological functions of the prostate gland that are regulated by testosterone and prolactin. The metabolic pathway for citrate production in the prostate involves the activity of mitochondrial aspartate aminotransferase (mAAT). The expression of mAAT in the prostate is regulated by prolactin through a signal transduction pathway mediated by protein kinase C (PKC). In this report we determined which PKC isoforms are expressed in rat lateral prostate epithelial cells and their activation by prolactin. Eight PKC isoforms are expressed in the ventral and lateral prostate lobes. Although all eight isoforms are expressed, only PKCalpha and PKCvarepsilon were stimulated by prolactin and only in the lateral prostate lobe. Activator protein-1 (AP-1) appears to be the target of prolactin-PKC signaling because prolactin stimulated nuclear protein binding to an AP-1 consensus oligodeoxynucleotide. Moreover, the nuclear binding protein stimulated by prolactin also bound an mAAT oligodeoxynucleotide that contained an AP-1 consensus sequence and which competed for binding with the consensus AP-1 oligodeoxynucleotide. A PKCvarepsilon antisense oligodeoxynucleotide blocked expression of mAAT mRNA. Thus, we conclude that PKCvarepsilon is a specific PKC isoform that mediates via AP-1 the signal for prolactin regulation of mAAT gene expression in rat lateral prostate epithelial cells.
Franklin
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RB
University of Maryland, Dental School, 666 West Baltimore Street, Room 4-E-36A, Baltimore, MD 21201, USA. rfrankli@umaryland.edu
Zou
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Ma
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Costello
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LC
D000818:Animals; D000906:Antibodies; D001219:Aspartate Aminotransferases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D007527:Isoenzymes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D011388:Prolactin / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D011493:Protein Kinase C / Q000494:pharmacology*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000494:pharmacology*
D000906:Antibodies; D007527:Isoenzymes; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D011388:Prolactin; D001219:Aspartate Aminotransferases; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon