Janus kinase 2 and calcium are required for angiotensin II-dependent activation of steroidogenic acute regulatory protein transcription in H295R human adrenocortical cells.
Angiotensin II- and K+-stimulated aldosterone production in the adrenocortical glomerulosa cells requires induction of the steroidogenic acute regulatory protein (StAR). While both agents activate Ca2+ signaling, the mechanisms leading to aldosterone synthesis are distinct, and the angiotensin II response cannot be mimicked by K+. We previously reported that StAR mRNA levels and promoter-reporter gene activity in transiently transfected H295R human adrenocortical cells were stimulated by angiotensin II but not by K+ treatment. The current study focused on identifying signaling pathways activated by angiotensin II that contribute to StAR transcriptional activation. We show that the angiotensin II-stimulated transcriptional activation of StAR was dependent upon influx of external calcium and requires protein kinase C activation. Furthermore we describe for the first time that the Janus tyrosine kinase family member, JAK2, was activated by angiotensin II treatment of H295R cells. Treatment of the cells with AG490, a selective inhibitor of JAK2, blocked JAK2 activation and StAR reporter gene activity and inhibited steroid production. Taken together these studies describe a novel pathway controlling StAR expression and steroidogenesis in adrenocortical cells.
Li
Jianghong
J
Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, Kentucky 40292, USA.
Feltzer
Rhona E
RE
Dawson
Kevin L
KL
Hudson
Elizabeth A
EA
Clark
Barbara J
BJ
D000302:Adrenal Cortex / Q000166:cytology*; D000804:Angiotensin II / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D017930:Genes, Reporter; D006801:Humans; D015151:Immunoblotting; D053614:Janus Kinase 2; D008156:Luciferases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020032:Tyrphostins / Q000494:pharmacology; D000098682:Steroidogenic Acute Regulatory Protein
D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D005419:Flavonoids; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D000098682:Steroidogenic Acute Regulatory Protein; D000804:Angiotensin II; D011374:Progesterone; D008156:Luciferases; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium