ArticleScientific reports2018
Conformational Landscape of the PRKACA-DNAJB1 Chimeric Kinase, the Driver for Fibrolamellar Hepatocellular Carcinoma.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma.Cell reports · 2024Article
- Fighting rare cancers: lessons from fibrolamellar hepatocellular carcinoma.Nature reviews. Cancer · 2023Review
- Biochemical Discovery, Intracellular Evaluation, and Crystallographic Characterization of Synthetic and Natural Product Adenosine 3',5'-Cyclic Monophosphate-Dependent Protein Kinase A (PKA) Inhibitors.ACS pharmacology & translational science · 2023Article
- Article
- A framework for fibrolamellar carcinoma research and clinical trials.Nature reviews. Gastroenterology & hepatology · 2022Review
- Association between genome-wide epigenetic and genetic alterations in breast cancer tissue and response to HER2-targeted therapies in HER2-positive breast cancer patients: new findings and a systematic review.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- The cAMP-signaling cancers: Clinically-divergent disorders with a common central pathway.Frontiers in endocrinology · 2022Review
- Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A.Communications biology · 2021Article
- Article
- Modulation of polycystic kidney disease by G-protein coupled receptors and cyclic AMP signaling.Cellular signalling · 2020Review
- Structures of the PKA RIα Holoenzyme with the FLHCC Driver J-PKAcα or Wild-Type PKAcα.Structure (London, England : 1993) · 2019Article
- The Molecular Basis for Specificity at the Level of the Protein Kinase a Catalytic Subunit.Frontiers in endocrinology · 2018Review
- Therapeutic Efficacy of Temsirolimus in a Patient-derived Model of Metastatic Fibrolamellar Hepatocellular Carcinoma.In vivo (Athens, Greece)Article
- Protein kinase C fusion proteins are paradoxically loss of function in cancer.The Journal of biological chemistryArticle
- Bilateral Adnexal Masses in a Young Female: Rare Presentation of Hepatocellular Carcinoma With Review of the Literature.Journal of clinical and experimental hepatologyArticle
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
In fibrolamellar hepatocellular carcinoma a single genetic deletion results in the fusion of the first exon of the heat shock protein 40, DNAJB1, which encodes the J domain, with exons 2-10 of the catalytic subunit of protein kinase A, PRKACA. This produces an enzymatically active chimeric protein J-PKAcα. We used molecular dynamics simulations and NMR to analyze the conformational landscape of native and chimeric kinase, and found an ensemble of conformations. These ranged from having the J-domain tucked under the large lobe of the kinase, similar to what was reported in the crystal structure, to others where the J-domain was dislodged from the core of the kinase and swinging free in solution. These simulated dislodged states were experimentally captured by NMR. Modeling of the different conformations revealed no obvious steric interactions of the J-domain with the rest of the RIIβ holoenzyme.
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