Role of protein kinases in neuropeptide gene regulation by PACAP in chromaffin cells: a pharmacological and bioinformatic analysis.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is an adrenomedullary cotransmitter that along with acetylcholine is responsible for driving catecholamine and neuropeptide biosynthesis and secretion from chromaffin cells in response to stimulation of the splanchnic nerve. Two neuropeptides whose biosynthesis is regulated by PACAP include enkephalin and vasoactive intestinal polypeptide (VIP). Occupancy of PAC1 PACAP receptors on chromaffin cells can result in elevation of cyclic AMP, inositol phosphates, and intracellular calcium. The proenkephalin A and VIP genes are transcriptionally responsive to signals generated within all three pathways, and potentially by combinatorial activation of these pathways as well. The characteristics of PACAP regulation of enkephalin and VIP biosynthesis were examined pharmacologically for evidence of involvement of several serine/threonine protein kinases activated by cAMP, IP3, and/or calcium, including calmodulin kinase II, protein kinase A, and protein kinase C. Evidence is presented for the differential involvement of these protein kinases in regulation of enkephalin and VIP biosynthesis in chromaffin cells, and for a prominent role of the mixed-function (tyrosine and serine/threonine) MAP kinase family in mediating transcriptional activation of neuropeptide genes by PACAP.
Hamelink
Carol
C
Section on Molecular Neuroscience, NIMH Intramural Research Program, Bethesda, Maryland 20892, USA.
Lee
Hyeon-Woo
HW
Hsu
Chang-Mei
CM
Eiden
Lee E
LE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D019295:Computational Biology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019992:Databases as Topic; D004745:Enkephalins / Q000096:biosynthesis; D005786:Gene Expression Regulation; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology*; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012984:Software; D013755:Tetradecanoylphorbol Acetate; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004745:Enkephalins; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D000242:Cyclic AMP; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium