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cAMP represses LPIN1 protein expression in human adrenocortical cells
Author(s) -
BetancourtTorres Andres,
Sewer Marion B.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.822.15
Subject(s) - diacylglycerol kinase , signal transduction , microbiology and biotechnology , nuclear export signal , biology , protein kinase a , nuclear localization sequence , protein kinase c , kinase , cytoplasm , cell nucleus
cAMP signaling induces cortisol production in adrenocortical cells by increasing the nuclear production of phosphatidic acid (PA), a ligand for the nuclear receptor steroidogenic factor 1 (SF‐1). Nuclear production of PA is dependent on diacylglycerol kinase theta (DGKQ), which catalyzes the conversion of diacylglycerol (DAG) to PA. Given that cAMP signaling saincreases DGKQ‐dependent PA production, we sought to determine the role of the cAMP signal transduction cascade in the catabolism of PA. Lipins (LPINs) are a family of PA phosphatases that dephosphorylate PA, thereby forming DAG. Thus, we treated H295R human adrenocortical cells with dibutyryl cAMP (dbcAMP) and assessed the effect on LPIN expression. We found that dbcAMP decreased the protein expression of LPIN1, with no significant effect on the mRNA expression of this gene. Further, the dbcAMP‐mediated decrease in LPIN1 protein expression was dependent on protein kinase A, suggesting a role for cAMP signaling in the stimulating the degradation of LPIN1. Finally, we show that LPIN1 is expressed in the both cytoplasmic and nuclear compartments of H295R cells and that cAMP signaling promotes the import of LPIN1 into the nucleus. Collectively, our studies identify a novel role for the cAMP signaling pathway in regulating the subcellular localization and stability of LPIN1 in the adrenal cortex. This project is supported by NIH DK084178.