Article
Biology
Gary K. L. Chan, Samantha Maisel, Yeonjoo C. Hwang, Bryan C. Pascual, Rebecca R. B. Wolber, Phuong Vu, Krushna C. Patra, Mehdi Bouhaddou, Heidi L. Kenerson, Huat C. Lim, Donald Long, Raymond S. Yeung, Praveen Sethupathy, Danielle L. Swaney, Nevan J. Krogan, Rigney E. Turnham, Kimberly J. Riehle, John D. Scott, Nabeel Bardeesy, John D. Gordan
Summary: Genetic alterations that activate protein kinase A (PKA) are found in many tumor types. The downstream oncogenic signaling mechanisms of PKA activation in human cancer were explored using phosphoproteomics and kinase activity profiling. Two signaling networks, RAS/MAPK components and an AURKA/GSK3 sub-network, were identified, both affecting MYC oncoproteins. Primary mechanism of PKA effects on MYC was found to be translation, which could be blocked with the eIF4A inhibitor zotatifin, suggesting a potential treatment strategy for PKA-driven cancers.
Review
Cell Biology
Anne-Sophie Colombe, Guillaume Pidoux
Summary: The cAMP signaling pathway plays a key role in regulating cardiac function under physiological conditions, but chronic activation can be deleterious, especially post-myocardial infarction. Temporal regulation depends on the activity of ACs and phosphodiesterases, while spatial and temporal regulation is coordinated by AKAPs.
Article
Pharmacology & Pharmacy
Yan Li, Kuiliang Zhang, Jinxin Liu, Shengnan Liu, Chenzhipeng Nie, Ying Yan, Yanming Guan, Mingcong Fan, Haifeng Qian, Hao Ying, Li Wang
Summary: Geniposide has been found to reduce body temperature and cold tolerance of mice by suppressing thermogenic genes in interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT). Additionally, geniposide suppresses thermogenic capacity of adipocytes in vitro and inhibits uncoupling protein 1 (UCP1) via regulating protein kinase A (PKA) signaling.
Article
Chemistry, Physical
Shaoshuai Zhou, Wei Wang, Xiantao Wei, Min Yin
Summary: By employing a time-gated ratiometric thermometry technique, the temperature was measured based on the luminescence intensity ratio. Sm3+ doped material was used as the temperature responsive signal and reference signal. The experimental results showed high relative sensitivity and good temperature measurement performance within the investigated temperature range.
JOURNAL OF ALLOYS AND COMPOUNDS
(2022)
Article
Cell Biology
Xiaokan Zhang, Bryan Z. Wang, Michael Kim, Trevor R. Nash, Bohao Liu, Jenny Rao, Roberta Lock, Manuel Tamargo, Rajesh Kumar Soni, John Belov, Eric Li, Gordana Vunjak-Novakovic, Barry Fine
Summary: Protein kinase A (PKA) is critical for cardiac function, but its activity is tightly regulated. In this study, we identified STK25 as a kinase of PRKAR1A, a regulatory subunit of PKA. Phosphorylation of PRKAR1A inhibits PKA activity and increases binding to the catalytic subunit. Knockout of Stk25 in mice leads to decreased Prkar1a phosphorylation, increased Pka activity, and enhanced response to beta-adrenergic stimulation. These findings suggest that STK25 acts as a negative regulator of PKA signaling through phosphorylation of PRKAR1A.
Article
Biology
Colin L. Welsh, Abigail E. Conklin, Lalima K. Madan
Summary: Understanding the changes in protein shape during cellular function is crucial for understanding biology. In this study, the researchers investigated the protein PKA and how its shape changes as it chemically alters other proteins. Using crystal structures of PKA, they identified regions that change shape based on interactions with ligands or other signaling proteins. These findings provide insight into PKA and protein kinase regulation, which can lead to advances in pharmacological therapies and disease biology.
Article
Biochemistry & Molecular Biology
Grace E. Peng, Veronica Pessino, Bo Huang, Mark von Zastrow
Summary: This study investigates how cAMP produced by endosomes regulates signaling to the nucleus, revealing that the key location-dependent step for endosome-encoded transcriptional control is the nuclear entry of cAMP-dependent protein kinase (PKA) catalytic subunits.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biology
Jeannette Delva-Wiley, Ese S. Ekhator, Laquaundra L. Adams, Supriya Patwardhan, Ming Dong, Robert H. Newman
Summary: The effects of oxidation on the activity of PKA-C α towards different substrates were investigated in this study. The results showed that oxidation differentially affects the activity of PKA-C α towards different substrates. This study provides novel insights into the crosstalk between redox- and phosphorylation-dependent signaling pathways mediated by PKA and lays the foundation for future studies on the role of redox-dependent modification of kinase substrate selection in physiological and pathological states.
Review
Pharmacology & Pharmacy
Edra London, Constantine A. A. Stratakis
Summary: The cAMP-dependent protein kinase (PKA) system plays a crucial role in cell signaling and is involved in cellular metabolism, emotional and stress responses, and energy homeostasis. It is regulated by neural and peripheral signals and affects various metabolic organs. Dysregulation of the PKA system can lead to metabolic diseases, and variants in PKA subunit genes are associated with Cushing syndrome. Understanding the sex differences in PKA signaling is important for understanding the physiological consequences of metabolic dysregulation and obesity. Exploring the regulation and targets of the PKA signaling pathway can offer potential therapeutic approaches for metabolic diseases.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Ikhyun Jun, Young Joon Choi, Bo-Rahm Kim, Kyoung Yul Seo, Tae-im Kim
Summary: This study discovered that activation of the ADRB2/PKA signaling pathway enhances lipid synthesis in human meibomian gland epithelial cells (HMGECs), providing a potential mechanism and therapeutic target for meibomian gland dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Xihua Yue, Yi Qian, Lianhui Zhu, Bopil Gim, Mengjing Bao, Jie Jia, Shuaiyang Jing, Yijing Wang, Chuanting Tan, Francesca Bottanelli, Pascal Ziltener, Sunkyu Choi, Piliang Hao, Intaek Lee
Summary: ACBD3 may regulate KDEL receptor trafficking by modulating Arf1-dependent tubule formation. Depletion of ACBD3 leads to re-localization of KDEL receptor to the ER through accelerated retrograde trafficking. This is caused by altering KDEL receptor interaction with Protein Kinase A and Arf1/ArfGAP1, resulting in increased Arf1-GTP-dependent tubular carrier formation at the Golgi.
Article
Chemistry, Analytical
Yundi Huang, Bo Song, Kaiwen Chen, Deshu Kong, Jingli Yuan
Summary: This study developed two lysosome-targetable background-free TGL probes for efficient and accurate detection of 1O2, which can be used for monitoring endogenous 1O2 concentrations in lysosomes and discriminating variability induced by different photosensitizers. Furthermore, a smart luminescent sensor film was successfully prepared for on-site 1O2 production detection during PDT processes, offering a promising clinical monitoring tool for skin diseases.
ANALYTICA CHIMICA ACTA
(2024)
Article
Cardiac & Cardiovascular Systems
Kathryn G. Helmstadter, Senka Ljubojevic-Holzer, Brent M. Wood, Khanha D. Taheri, Simon Sedej, Jeffrey R. Erickson, Julie Bossuyt, Donald M. Bers
Summary: The study uncovered the interplay of CaMKII and PKA in regulating HDAC4 phosphorylation and translocation in adult cardiomyocytes. Under physiological conditions, PKA drives HDAC4 into the nucleus while CaMKII leads to HDAC4 export to the cytoplasm. However, in failing cardiomyocytes, CaMKII-dependent effects predominate.
BASIC RESEARCH IN CARDIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Matthias Oebbeke, Christof Siefker, Bjoern Wagner, Andreas Heine, Gerhard Klebe
Summary: In medicinal chemistry optimization, strategies involve replacing functional groups and attaching larger substituents at a promising lead scaffold. While bioisosterism rules are considered, it is challenging to determine whether the introduced modifications match the required properties at a binding site. Modulating electron density distribution and pK(a) values can influence protonation states and bioavailability. The importance lies in correctly designing pK(a) values of attached functional groups at the parent scaffold.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Lin Zhu, Ting Gao, Yi Huang, Jing Jin, Di Wang, Leike Zhang, Yanwen Jin, Ping Li, Yong Hu, Yan Wu, Hainan Liu, Qincai Dong, Guangfei Wang, Tong Zheng, Caiwei Song, Yu Bai, Xun Zhang, Yaoning Liu, Weihong Yang, Ke Xu, Gang Zou, Lei Zhao, Ruiyuan Cao, Wu Zhong, Xianzhu Xia, Gengfu Xiao, Xuan Liu, Cheng Cao
Summary: The Ebola virus VP35 protein uses the host PKA-CREB1 signaling pathway for viral replication and pathogenesis, and upregulates the transcription of coagulation-related genes, potentially leading to hemorrhage.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Victoriia Murina, Marje Kasari, Vasili Hauryliuk, Gemma C. Atkinson
NUCLEIC ACIDS RESEARCH
(2018)
Article
Biochemistry & Molecular Biology
Jurgen Vahter, Kaido Viht, Asko Uri, Ganesh Babu Manoharan, Erki Enkvist
BIOORGANIC & MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Markus Pietsch, Kaido Viht, Alexander Schnitzler, Ramesh Ekambaram, Michaela Steinkrueger, Erki Enkvist, Christian Nienberg, Anna Nickelsen, Miriam Lauwers, Joachim Jose, Asko Uri, Karsten Niefind
BIOORGANIC CHEMISTRY
(2020)
Editorial Material
Pharmacology & Pharmacy
Asko Uri, Olivier Etebe Nonga
EXPERT OPINION ON DRUG DISCOVERY
(2020)
Article
Biochemistry & Molecular Biology
Olivier Etebe Nonga, Darja Lavogina, Taavi Ivan, Kaido Viht, Erki Enkvist, Asko Uri
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2020)
Article
Chemistry, Organic
Marek Kollo, Marje Kasari, Villu Kasari, Tonis Pehk, Ivar Jarving, Margus Lopp, Arvi Joers, Tonis Kanger
Summary: The method described in this article synthesizes 9,11-secosteroids from natural corticosteroid cortisol, utilizing both biocatalysis and chemical reactions. This approach offers mild reaction conditions and eliminates the need for toxic oxidants.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Optics
Ines G. Tavares, Erki Enkvist, Joosep Kaimre, Asko Uri, Fernando B. Dias
Summary: This work investigates the intramolecular energy transfer between two thiophene donors and a perylene bisimide acceptor, demonstrating the transfer of energy from the thiophene donor's excited triplet state to the perylene bisimide acceptor's singlet state. The designed organic luminophore, ARC-1467, shows delayed fluorescence of perylene bisimide upon excitation of the donor unit, indicating the occurrence of energy transfer from the triplet state of the donor unit to the perylene bisimide acceptor.
JOURNAL OF LUMINESCENCE
(2021)
Article
Obstetrics & Gynecology
Darja Lavogina, Artjom Stepanjuk, Maire Peters, Kulli Samuel, Sergo Kasvandik, Masuma Khatun, Riikka K. Arffman, Erki Enkvist, Kaido Viht, Sergei Kopanchuk, Freddy Lattekivi, Agne Velthut-Meikas, Asko Uri, Terhi T. Piltonen, Ago Rinken, Andres Salumets
Summary: The study identified elevated ROCK activity in response to combined progesterone and 8-Br-cAMP treatment during in vitro decidualization, leading to increased ROCK2 mRNA and protein levels as well as phosphorylation of its downstream target Cofilin-1. This research highlighted the importance of ROCK as a novel target in decidualization and the need for further investigation, especially in the context of subfertility and infertility related to decidualization.
HUMAN REPRODUCTION
(2021)
Article
Biochemistry & Molecular Biology
Olivier E. Nonga, Darja Lavogina, Erki Enkvist, Katrin Kestav, Apirat Chaikuad, Sarah E. Dixon-Clarke, Alex N. Bullock, Sergei Kopanchuk, Taavi Ivan, Ramesh Ekambaram, Kaido Viht, Stefan Knapp, Asko Uri
Summary: The X-ray crystallographic study of PIM-1 protein kinase complexes with three inhibitors revealed simplified chemical structures with reduced polar groups and chiral centers, which showed low-nanomolar potency and high selectivity towards PIM kinases. The developed inhibitors were functionalized with biotin or fluorescent dye Cy5 for detection in biochemical solutions and complex biological samples. Utilizing a PIM-2 selective detection antibody, a sandwich assay was able to detect as low as 44 pg of active recombinant PIM-2.
Article
Chemistry, Medicinal
Tanel Sormus, Darja Lavogina, Anu Teearu, Erki Enkvist, Asko Uri, Kaido Viht
Summary: This study reports the development of the first covalent bisubstrate PK inhibitor that reacts with a distant cysteine residue outside the ATP-binding site. The synthesized inhibitors demonstrated PKA-selectivity and targeting capability in cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Darja Lavogina, Naila Nasirova, Tanel Sormus, Taavo Tahtjarv, Erki Enkvist, Kaido Viht, Toiv Haljasorg, Koit Herodes, Jana Jaal, Asko Uri
Summary: In this research, we designed a series of ARCs and their fluorescent derivatives to investigate their interactions with members of the protein arginine methyltransferase (PRMT) family. Our results showed that ARCs and arginine-rich peptides could serve as high-affinity ligands for PRMT1, and the equilibrium dissociation constant values were dependent on the number of arginine residues within the compounds.
JOURNAL OF PEPTIDE SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Tanel Sormus, Darja Lavogina, Erki Enkvist, Asko Uri, Kaido Viht
Summary: Bivalent ligands, such as bisubstrate inhibitors, can simultaneously target two binding sites of a biomolecule and their ability to bind to the biological target can be modulated by an external trigger. This study constructed deactivatable bisubstrate inhibitors of basophilic protein kinases by conjugating pharmacophores via linkers that can be cleaved in response to external stimuli. The inhibitors exhibited high affinity and inhibitory potency towards cAMP-dependent PK (PKAc alpha), which could be reduced by specific external stimuli. These deactivatable inhibitors are valuable tools for the inhibition or capture of pharmacologically important enzymes.
Article
Chemistry, Multidisciplinary
Tanel Sormus, Darja Lavogina, Erki Enkvist, Asko Uri, Kaido Viht
CHEMICAL COMMUNICATIONS
(2019)
Article
Materials Science, Multidisciplinary
Joana Jogela, Asko Uri, Lars-Olof Palsson, Erki Enkvist
JOURNAL OF MATERIALS CHEMISTRY C
(2019)
Article
Biochemistry & Molecular Biology
Juergen Vahter, Kaido Viht, Asko Uri, Erki Enkvist
BIOORGANIC & MEDICINAL CHEMISTRY
(2017)
Article
Biochemical Research Methods
Saranya Krishnan, Shina Sasi, Preshobha Kodakkattumannil, Salima Al Senaani, Geetha Lekshmi, Martin Kottackal, Khaled M. A. Amiri
Summary: This study aimed to develop an efficient DNA extraction protocol suitable for diverse plant species and tissues. A reliable and consistent protocol was described for the extraction of high-quality DNA from difficult-to-extract plant species. The optimized protocol was successful in extracting high-quality DNA from various plant species and tissues, making it useful for genomic studies of recalcitrant plants.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Eisaku Hokazono, Saori Fukumoto, Takeshi Uchiumi, Susumu Osawa
Summary: This study proposes a method for detecting nucleic acid amplification using pyrophosphate, which requires only two reagents and an automated analyzer. The technique has high sensitivity and reproducibility, and can detect pyrophosphate within 10 minutes. Therefore, this method has the potential to be a new, rapid, and simple detection technique for amplified nucleic acids.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Drew S. Sowersby, L. Kevin Lewis
Summary: SURE electrophoresis is a new method for concentrating samples in gels, which allows efficient detection of highly dilute DNA samples. This approach generates single bands with enhanced signal intensities and minimal band broadening.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Hongyi Liang, Guoliang Yin, Guangxi Shi, Zhiyong Liu, Xiaofei Liu, Jingwei Li
Summary: The mechanism of Echinacoside (ECH) in treating breast cancer (BC) was explored through network pharmacology and experimental validation. It was found that ECH plays an important role in anti-BC by regulating the PI3K/AKT/HIF-1 alpha/VEGF signaling pathway, and it exhibits multi-target and multi-pathway effects.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Daniel S. Kantner, Emily Megill, Anna Bostwick, Vicky Yang, Carmen Bekeova, Alexandria Van Scoyk, Erin L. Seifert, Michael W. Deininger, Nathaniel W. Snyder
Summary: This study compared the results of different methods for measuring the amount of acetyl-Coenzyme A. The colorimetric ELISA kit did not produce interpretable results, while the fluorometric enzymatic kit showed comparable results to the LC-MS-based methods depending on the matrix and extraction conditions. LC-MS/MS and LC-HRMS methods produced well-aligned results, especially when using stable isotope-labeled internal standards.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Jingyan Xu, Hanying Tan, Xionghui Ma, Linjing Su, Zhi Zhang, Yuhao Xiong
Summary: This study investigates the co-catalytic capabilities of MoO3 nanosheets in enhancing the enzyme-like catalytic activity of a two-dimensional ultrathin Fe(III)-modified covalent triazine framework (Fe-CTF) under neutral pH conditions. The Fe-CTF/MoO3 co-catalytic system exhibits enzyme-mimicking activity and enables the development of a colorimetric method for glucose detection. Furthermore, a straightforward one-pot colorimetric method is established for screening XOD inhibitors.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Lichao Zhang, Kang Xiao, Xueting Wang, Liang Kong
Summary: A novel fusion technology was designed to identify FAD-binding sites, achieving the best results on two independent test datasets and outperforming existing methods significantly. The high performance and certainty of the method were demonstrated through statistical tests and cross-entropy loss analysis.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Abdulkadir Kilic, Mehmet Aslan, Abdulkadir Levent
Summary: This study developed a simple, rapid, sensitive, and selective voltammetric technique for the electrochemical characterization and detection of the highly risky drug Edoxaban. The optimized voltammetric method showed good analytical working range and was successfully applied to urine and tablet samples.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Su Hyun Kim, Nara Shin, Jong-Min Jeon, Jeong-Jun Yoon, Jeong Chan Joo, Hee Taek Kim, Shashi Kant Bhatia, Yung-Hun Yang
Summary: To address environmental issues caused by traditional plastics, bioplastics have gained attention as alternatives. Although bioplastics have better degradability, their degradation still takes longer than anticipated. This study proposes a novel screening method to identify bioplastic degraders faster, saving time and providing more quantitative data.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Irem Okman Kocoglu, Pinar Esra Erden, Esma Kilic
Summary: In this study, an electrochemical biosensor based on carbon nanofibers and ionic liquid modification was constructed for tyramine detection. The biosensor showed linear response, low detection limit, high sensitivity, and exhibited good reproducibility, stability, and anti-interference ability.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Liana U. Akhmetzianova, Timur M. Davletkulov, Assol R. Sakhabutdinova, Alexey Chemeris, Irek M. Gubaydullin, Ravil R. Garafutdinov
Summary: A new program called LAMPrimers iQ has been developed for high-quality LAMP primer design, and its advantages in providing higher specificity and reliable detection of viral RNA were validated using SARS-CoV-2 coronavirus RNA as a model target.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Tommaso Pileri, Alberto Sinibaldi, Agostino Occhicone, Norbert Danz, Elena Giordani, Matteo Allegretti, Frank Sonntag, Peter Munzert, Patrizio Giacomini, Francesco Michelotti
Summary: This study developed a biosensing device based on one-dimensional photonic crystal to detect HER2 in breast cancer. The device combines label-free and fluorescence operation modes, allowing for real-time and accurate detection in less than 20 minutes. It offers a promising technique for combined label-free and fluorescence detection in disease diagnosis and therapeutic monitoring.
ANALYTICAL BIOCHEMISTRY
(2024)