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Overexpression of PKA regulatory subunits in ovarian cancer cells

ABSTRACT: The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Keywords: genetic modification

ORGANISM(S): Homo sapiens

PROVIDER: GSE12854 | GEO | 2008/09/20

SECONDARY ACCESSION(S): PRJNA111087

REPOSITORIES: GEO

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Transcription profiling by array of human ovarian cancer cells overexpressing PKA regulatory subunits

Project description:The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. RI? transfected cells exhibit hyper-proliferative growth and RII? transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RI?, RII?, and parental OVCAR cells.

2008-10-25 | E-GEOD-12854 | biostudies-arrayexpress

Discovery of a new Cushing’s syndrome PKAc mutant that is retained within anchored type I holoenzymes

Project description:Adrenal Cushing’s syndrome is a disease of cortisol hypersecretion often caused by mutations in protein kinase A catalytic subunit (PKAc). Using a personalized medicine screening platform, we discovered a new Cushing’s driver mutation, PKAc-W196G, in ~20% of patient samples analyzed. Proximity proteomics and photokinetic imaging reveal that PKAcW196G is distinct from other Cushing’s variants. This mutant surprisingly retains association with type I regulatory subunits (RI) and their corresponding A kinase anchoring proteins (AKAPs). Molecular dynamics simulations predict that substitution of glycine for tryptophan 196 creates a 653 Å3 cleft between the catalytic core of PKAcW196G and type II regulatory subunits (RII), but only a 395 Å3 cleft with RI. Endocrine measurements show that overexpression of RIα or redistribution of PKAcW196G via AKAP recruitment counteracts stress hormone overproduction. We conclude that a W196G mutation in the kinase catalytic core skews R subunit selectivity and biases AKAP association to drive Cushing’s syndrome.

2024-02-10 | PXD045556 | Pride

PKA regulated genes in HEK293 cells

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Exploring the scope of TOR/PKA co-regulation in MDN

Project description:To identify genes co-regulated by TOR and PKA during growth in MDN Keywords: Media, Wild type and mutant strains, and dose response

2005-08-19 | GSE3160 | GEO

TORC1 and PKA dependent gene regulation

Project description:To determine how TORC1 and PKA cooperate to regulate cell growth, we performed temporal analysis of gene expression in yeast switched from a non-fermentable substrate, to glucose, in the presence and absence of TORC1 and PKA inhibitors. Quantitative analysis of these data reveals that PKA drives the expression of key cell growth genes during transitions into, and out of, the rapid growth state in glucose, while TORC1 is important for the steady-state expression of the same genes.

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Expression data from the mushroom bodies of Drosophila-PKA activity dependent manner

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2014-03-25 | E-GEOD-28181 | biostudies-arrayexpress

A PKA/PP2A AXIS DRIVES THE GROWTH OF NEUROENDOCRINE SCLC

Project description:Small cell lung cancer (SCLC) is an aggressive subtype of lung cancer whose biology is still poorly understood. Using a multiplexed inhibitor beads assay, we identified active kinases in SCLC. Among those, we found that PKA is critical for the expansion of SCLC in culture and in vivo. PKA promotes the neuroendocrine epithelial state associated with SCLC tumor-initiating cells. Phosphoproteomics analyses identify ~200 PKA substrates and show that PKA controls multiple facets of SCLC growth. Notably, the PP2A phosphatase counteracts the oncogenic effects of PKA, and PP2A activators inhibit SCLC as single agents and with chemotherapy. Our data uncover key signaling networks in SCLC and indicate that targeting the PKA/PP2A pathway may help inhibit this lethal neuroendocrine cancer.

2020-02-11 | GSE126353 | GEO

Expression data from the mushroom bodies of Drosophila-PKA activity dependent manner

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2015-06-24 | E-GEOD-70216 | biostudies-arrayexpress

Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase 2A signaling in cardiac myocytes by nitroxyl

Project description:Sympathetic activation is the main driver of cardiac inotropy and lusitropy. Stimulation of the -adrenoceptor (AR) signaling cascade leads to activation of cAMP-dependent protein kinase (PKA) and subsequent cardiac protein phosphorylation, which is counteracted by the corresponding protein phosphatases 2A (PP2A). Both, kinase and phosphatase are sensitive to oxidation. For PKA, the oxidant-mediated mode of regulation has been described to occur by interdisulfide formation between type I regulatory subunits (PKA-RI). Furthermore, oxidant-mediated intradisulfide formation in the catalytic subunit of PKA and PP2A was shown to inhibit kinase or phosphatase activity, respectively. Nitroxyl donors exert positive inotropic and lusitropic effects in cardiac myocytes.

2020-10-29 | PXD019808 | Pride

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