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
Biochemistry & Molecular Biology
Jie Jia, Shuocheng Tang, Xihua Yue, Shuaiyang Jing, Lianhui Zhu, Chuanting Tan, Jingkai Gao, Yulei Du, Intaek Lee, Yi Qian
Summary: KDEL receptor (KDELR) is necessary for recycling ER resident proteins from the Golgi apparatus back to the ER, thus maintaining the balance between these two organelles. ACBD3 and PKA have been shown to regulate this process, but their interaction and coordination at the Golgi have not been fully understood. In this study, it was revealed that ACBD3 directly interacts with the regulatory subunit II (RII) of PKA at the Golgi and recruits PKA to this organelle. Depletion of ACBD3 leads to constitutive activation of PKA and increased retrograde transport of KDELR. These findings highlight the role of ACBD3 in coordinating protein secretion at the Golgi.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
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
Multidisciplinary Sciences
Isabel Weigand, Cristina L. Ronchi, Jens T. Vanselow, Kerstin Bathon, Kerstin Lenz, Sabine Herterich, Andreas Schlosser, Matthias Kroiss, Martin Fassnacht, Davide Calebiro, Silviu Sbiera
Summary: Mutations in the PRKACA gene are a common cause of cortisol-producing adrenocortical adenomas and Cushing's syndrome, affecting the binding of regulatory subunits and leading to reduced RII β protein levels. The study shows that phosphorylation of RII β at Ser(114) is necessary for its degradation, mediated by caspase 16, resulting in increased cortisol secretion in adrenocortical cells. These findings provide insight into the molecular mechanisms and pathophysiological relevance of R subunit degradation caused by PRKACA mutations in adrenal Cushing's syndrome.
Article
Biology
Juan Qin, Jingfeng Zhang, Lianyun Lin, Omid Haji-Ghassemi, Zhi Lin, Kenneth J. Woycechowsky, Filip Van Petegem, Yan Zhang, Zhiguang Yuchi
Summary: This study reveals the disease mechanism of several mutations in PLN by changing its conformation and weakening its interaction with PKA, leading to the reduction of its phosphorylation level. Additionally, another regulatory peptide, called ALN, also regulates SERCA activity through a similar mechanism mediated by PKA.
Article
Biochemistry & Molecular Biology
Heather R. Dahlin, Ning Zheng, John D. Scott
Summary: Protein-interaction domains, specifically the docking and dimerization (D/D) domain, play a crucial role in cell signaling and are highly conserved. Analysis has revealed that D/D domain proteins can be classified into different subgroups based on their similarity to PKA regulatory subunits. Research has shown that the D/D fold maintains the integrity of cellular structures.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Microbiology
Mei-Chen Zhu, Na Zhao, Yan-Kun Liu, Xue-Mei Li, Zheng-Yi Zhen, Ya-Qing Zheng, Ke-Qin Zhang, Jin-Kui Yang
Summary: The cAMP-PKA signalling pathway plays a crucial role in regulating various biological processes in Arthrobotrys oligospora, including hyphal growth, trap morphogenesis, sporulation, stress resistance, autophagy, and mitochondrial morphology.
ENVIRONMENTAL MICROBIOLOGY
(2022)
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.
Article
Cell Biology
Darko Maric, Aleksandra Paterek, Marion Delaunay, Irene Perez Lopez, Miroslav Arambasic, Dario Diviani
Summary: The study demonstrates that AKAP2 plays a role in promoting cardioprotection in infarcted hearts, with its knockout leading to increased infarct size and worsened cardiac function. AKAP2 forms a complex with PKA and Src3 in cardiomyocytes, facilitating the activation of ERα and upregulation of genes involved in anti-apoptosis and angiogenesis. Decreased AKAP2 expression results in increased myocardial apoptosis and impaired formation of new blood vessels in infarcted hearts.
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
Biochemistry & Molecular Biology
Yuening Liu, Jingrui Chen, Peng Xia, Constantine A. Stratakis, Zhaokang Cheng
Summary: The loss of R1 alpha may lead to unrestrained PKA activation and impairment of the mTORC1-p62-Keap1-Nrf2 antioxidant defense system, resulting in exacerbated myocardial injury caused by ischemia/reperfusion. This discovery provides a new potential pathway for the development of new cardioprotective therapies.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Nicholas C. Vierra, Luisa Ribeiro-Silva, Michael Kirmiz, Deborah van der List, Pradeep Bhandari, Olivia A. Mack, James Carroll, Elodie Le Monnier, Sue A. Aicher, Ryuichi Shigemoto, James S. Trimmer
Summary: Neuronal ER-PM junctions support a receptor-independent form of PKA signaling, driven by membrane depolarization and intracellular Ca2+, allowing conversion of information encoded in electrical signals into biochemical changes recognized throughout the cell.
NATURE COMMUNICATIONS
(2023)
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.
Review
Pharmacology & Pharmacy
Kinjal Patel, Nicola J. Smith
Summary: Primary cilia are important for sensing environmental changes in mammalian cells through the Sonic Hedgehog pathway. GPR161 is a significant player in primary cilia and its unique features may affect receptor function and cAMP compartmentalisation. The recent potential pairing of GPR161 and spexin-1 requires further investigation before GPR161 is considered 'deorphanised'. The constitutive activity and unconventional regulation of GPR161 suggest that it may not require an endogenous ligand.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)