Growth hormone increases regulator of calcineurin 1-4 (Rcan1-4) mRNA through c-JUN in rat liver.
Animals
Gene Expression Regulation
/ drug effects
Growth Hormone
/ pharmacology
Intracellular Signaling Peptides and Proteins
/ genetics
JNK Mitogen-Activated Protein Kinases
/ metabolism
Liver
/ drug effects
Phosphorylation
/ drug effects
RNA, Messenger
/ genetics
Rats
Signal Transduction
/ drug effects
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
07
02
2020
accepted:
11
06
2020
entrez:
27
6
2020
pubmed:
27
6
2020
medline:
5
9
2020
Statut:
epublish
Résumé
Growth hormone (GH) activates multiple signal transduction pathways. To investigate these pathways, we identified novel genes whose transcription was induced by GH in the liver of hypophysectomized (HPX) rats using the suppression subtractive hybridization technique. We found that regulator of calcineurin 1 (Rcan1) mRNA was upregulated by GH administration. RCAN1 regulates the activity of calcineurin, a Ca/calmodulin-dependent phosphatase. Rcan1 encodes two major transcripts, Rcan1-1 and Rcan1-4, resulting from differential promoter use and first exon choice. We found that a single injection of GH increased the levels of Rcan1-4 mRNA and RCAN1-4 protein transiently, but did not increase Rcan1-1 mRNA in HPX rat liver. Then the molecular mechanism of GH to induce Rcan1-4 transcription was examined in rat hepatoma H4IIE cells. Experiments using inhibitors suggested that c-JUN N-terminal kinase was required for the induction of Rcan1-4 mRNA by GH. GH increased the levels of phosphorylated c-JUN protein and c-Jun mRNA in HPX rat liver. The luciferase and electrophoretic mobility shift assays showed that c-JUN upregulated Rcan1-4 mRNA by binding to the cAMP-responsive element in the upstream of Rcan1 exon 4. These results indicate that GH activates c-JUN to affect the activity of calcineurin by the induction of Rcan1-4 in rat liver.
Identifiants
pubmed: 32589657
doi: 10.1371/journal.pone.0235270
pii: PONE-D-20-03557
pmc: PMC7319343
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
RCAN1 protein, rat
0
RNA, Messenger
0
Growth Hormone
9002-72-6
JNK Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0235270Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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