ArticleHuman molecular genetics2014
mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD).
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
- Advances in Adipose Tissue Biology.Endocrine reviews · 2026Review
- Chlorogenic Acid Enhances Beta-Lapachone-Induced Cell Death by Suppressing Autophagy in NQO1-Positive Cancer Cells.Cell biology international · 2025Article
- Treatment of Primary Pigmented Nodular Adrenocortical Disease.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2022Review
- Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex.The Journal of clinical investigation · 2021Article
- Temporal Quantitative Profiling of Newly Synthesized Proteins during Aβ Accumulation.Journal of proteome research · 2021Article
- The mammalian target of rapamycin (mTOR) kinase mediates haloperidol-induced cataleptic behavior.Translational psychiatry · 2020Article
- Regulation of mTORC1 by Upstream Stimuli.Genes · 2020Review
- Illicit Upregulation of Serotonin Signaling Pathway in Adrenals of Patients With High Plasma or Intra-Adrenal ACTH Levels.The Journal of clinical endocrinology and metabolism · 2019Article
- The transient cortical zone in the adrenal gland: the mystery of the adrenal X-zone.The Journal of endocrinology · 2019Review
- miR-503 suppresses the proliferation and metastasis of esophageal squamous cell carcinoma by triggering autophagy via PKA/mTOR signaling.International journal of oncology · 2018Article
- Effect of beta-agonists on LAM progression and treatment.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Activation of D1R/PKA/mTOR signaling cascade in medial prefrontal cortex underlying the antidepressant effects of l-SPD.Scientific reports · 2017Article
- A siRNA screen reveals the prosurvival effect of protein kinase A activation in conditions of unresolved endoplasmic reticulum stress.Cell death and differentiation · 2016Article
- Activation of mTORC1 is essential for β-adrenergic stimulation of adipose browning.The Journal of clinical investigation · 2016Article
- Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases.Nature reviews. Rheumatology · 2016Review
- GATA factors in endocrine neoplasia.Molecular and cellular endocrinology · 2016Review
- Mouse Models Recapitulating Human Adrenocortical Tumors: What Is Lacking?Frontiers in endocrinology · 2016Review
- Toying with fate: Redirecting the differentiation of adrenocortical progenitor cells into gonadal-like tissue.Molecular and cellular endocrinology · 2015Review
- Neuron membrane trafficking and protein kinases involved in autism and ADHD.International journal of molecular sciences · 2015Review
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating mutations of the PRKAR1A tumor suppressor gene that encodes the regulatory subunit R1α of the cAMP-dependent protein kinase (PKA). In human and mouse adrenocortical cells, these mutations lead to increased PKA activity, which results in increased resistance to apoptosis that contributes to the tumorigenic process. We used in vitro and in vivo models to investigate the possibility of a crosstalk between PKA and mammalian target of rapamycin (mTOR) pathways in adrenocortical cells and its possible involvement in apoptosis resistance. Impact of PKA signaling on activation of the mTOR pathway and apoptosis was measured in a mouse model of PPNAD (AdKO mice), in human and mouse adrenocortical cell lines in response to pharmacological inhibitors and in PPNAD tissues by immunohistochemistry. AdKO mice showed increased mTOR complex 1 (mTORC1) pathway activity. Inhibition of mTORC1 by rapamycin restored sensitivity of adrenocortical cells to apoptosis in AdKO but not in wild-type mice. In both cell lines and mouse adrenals, rapid phosphorylation of mTORC1 targets including BAD proapoptotic protein was observed in response to PKA activation. Accordingly, BAD hyperphosphorylation, which inhibits its proapoptotic activity, was increased in both AdKO mouse adrenals and human PPNAD tissues. In conclusion, mTORC1 pathway is activated by PKA signaling in human and mouse adrenocortical cells, leading to increased cell survival, which is correlated with BAD hyperphosphorylation. These alterations could be causative of tumor formation.
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