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AKAP13 coordinates cAMP signaling and glucocorticoid production in H295R human adrenocortical cells (612.2)
Author(s) -
Escajadillo Tamara,
Sewer Marion
Publication year - 2014
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.28.1_supplement.612.2
Subject(s) - microbiology and biotechnology , rhoa , protein kinase a , signal transduction , mapk/erk pathway , adrenal cortex , kinase , endoplasmic reticulum , gene silencing , biology , chemistry , endocrinology , biochemistry , gene
The cAMP pathway activates steroid hormone biosynthesis in the adrenal cortex by regulating the activity of various proteins. We have previously identified a macromolecular protein complex that modulates cortisol biosynthesis by facilitating communication between the endoplasmic reticulum (ER) and mitochondria. One of the proteins in this complex is A‐kinase anchoring protein (AKAP)‐13. AKAPs play a critical role in the spatiotemporal compartmentalization of cAMP signaling, with AKAP13 being implicated in integrating Rho and cAMP‐dependent protein kinase A (PKA) signaling. AKAP13 has also been shown to regulate extracellular‐signal regulated kinase (ERK) and protein kinase D (PKD) activity in other cell types. We hypothesized that AKAP13 regulates cortisol production by coordinating RhoA and PKA signaling at the mitochondrial‐ER interface, and that disruption of AKAP13 leads to mislocalized cAMP signaling. We show that silencing AKAP13 in H295R human adrenocortical cells impairs cAMP‐stimulated RhoA, PKA and PKD phosphorylation and decreases cortisol and DHEA production. Consistent with previous findings, silencing AKAP13 had no effect on ERK activation or on the activation of hormone sensitive lipase. We conclude that AKAP13 is critical for the relay of cAMP signaling for cortisol production. Grant Funding Source : Supported by NIH DK094151.