Article
Biochemistry & Molecular Biology
Ranjana Maurya, Anuj Tripathi, Manish Kumar, Neelam Antil, Yoshiki Yamaryo-Botte, Praveen Kumar, Priyanka Bansal, Christian Doerig, Cyrille Y. Botte, T. S. Keshava Prasad, Pushkar Sharma
Summary: The study reveals that PfCDPK7 promotes phosphatidylcholine synthesis by regulating key enzymes involved in the process and interacts with 4'-phosphorylated phosphoinositides generated by PI4-kinase. Inhibition of PI4K disrupts the vesicular localization of PfCDPK7. Inhibitors of PfPI4K may control phospholipid biosynthesis through regulation of PfCDPK7 localization and activity.
Review
Biochemistry & Molecular Biology
Giulia Franciosa, Marie Locard-Paulet, Lars J. Jensen, Jesper Olsen
Summary: Mass spectrometry-based phosphoproteomics is the leading method for studying global kinase signaling. Various technological improvements and bioinformatic resources are available to accurately identify and quantify phosphopeptides, interpret large-scale data, and understand kinase network functional role. This review presents the latest experimental and bioinformatic tools for profiling protein kinase signaling networks and their applications in biomedicine.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Biology
Vidyasiri Vemulapalli, Lily A. Chylek, Alison Erickson, Anamarija Pfeiffer, Khal-Hentz Gabriel, Jonathan LaRochelle, Kartik Subramanian, Ruili Cao, Kimberley Stegmaier, Morvarid Mohseni, Matthew J. LaMarche, Michael G. Acker, Peter K. Sorger, Steven P. Gygi, Stephen C. Blacklow
Summary: The protein SHP2, often mutated in human cancer, potentiates intracellular signaling but can also have distinct effects when inhibited, as shown through phosphoproteome dynamics in breast cancer cells responding to EGF. Inhibiting SHP2 can lead to altered phosphorylation levels at specific tyrosine residues and highlight its dual roles as a scaffolding and catalytic protein in transmembrane signaling responses.
Article
Agronomy
Fengyi Gao, Liang Zhang, James R. Lloyd, Wenbin Zhou, Yanmei Chen
Summary: This article summarizes the complex functions of protein phosphorylation in plant metabolism and discusses how key kinases regulate carbohydrate metabolic pathways and their impact on plant physiology and crop quality.
Article
Oncology
Mahmoud Hallal, Sophie Braga-Lagache, Jovana Jankovic, Cedric Simillion, Remy Bruggmann, Anne-Christine Uldry, Ramanjaneyulu Allam, Manfred Heller, Nicolas Bonadies
Summary: Despite the limited predictive power of genomics in myeloid malignancies, a novel Kinase-Activity Enrichment Analysis (KAEA) pipeline was developed to analyze differential phosphoproteomics profiles. The KAEA pipeline successfully identified over- and under-active kinases in human myeloid cell lines and characterized targets of kinase-inhibitors. This approach provides researchers with an improved tool to study kinase behavior in response or resistance to targeted treatments.
Review
Cell Biology
Agnieszka Kilanowska, Agnieszka Ziolkowska, Piotr Stasiak, Magdalena Gibas-Dorna
Summary: The cAMP-dependent pathway plays a significant role in ovarian cells, regulating gene expression and cellular functions. It is associated with ovarian cancer development, metastasis, and survival. Targeting specific stages of this pathway may offer promising therapeutic opportunities for ovarian cancer patients.
Article
Plant Sciences
Robin Lardon, Hoang Khai Trinh, Xiangyu Xu, Lam Dai Vu, Brigitte van de Cotte, Marketa Pernisova, Steffen Vanneste, Ive De Smet, Danny Geelen
Summary: The reversible protein phosphorylation in plants plays a vital role in shoot organogenesis. The study shows that the histidine kinase inhibitor TCSA can impede cytokinin signal transduction and affect regeneration. The phosphoproteome analysis reveals the deregulation of various phosphoproteins involved in protein modification, transcription, organ morphogenesis, and cation transport.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemical Research Methods
Kenneth I. Onyedibe, Rodrigo Mohallem, Modi Wang, Uma K. Aryal, Herman O. Sintim
Summary: CDNs such as 2' 3'-cGAMP activate TBK1 to bind with STING, triggering the production of cytokines and interferons. STING activation by CDN also leads to the release and activation of NF-kappa B via the phosphorylation of I kappa B alpha by IKK. This study reveals the broad effects of 2' 3'-cGAMP on global phosphorylation events and identifies different kinase signatures associated with cell response to this second messenger.
JOURNAL OF PROTEOMICS
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Yun Qin, Stefan Imobersteg, Stephan Frank, Alain Blanc, Tanja Chiorazzo, Philipp Berger, Roger Schibli, Martin P. Behe, Michal Grzmil
Summary: α-particle emitters have potential as therapeutic radionuclides, but toxicity and radioresistance limit their efficacy. This study identified the radiation-activated mechanisms driving cancer cell survival, providing opportunities for therapeutic interference to improve the efficacy and safety of α-particle therapy.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Panshak P. P. Dakup, Song Feng, Tujin Shi, Jon M. Jacobs, H. Steven Wiley, Wei-Jun Qian
Summary: Post-translational modifications (PTMs), especially phosphorylation, play a crucial role in regulating protein function. Traditional immunological assays often lack sensitivity and specificity for quantitative measurements of protein phosphorylation. Recent advances in Mass Spectrometry (MS)-based targeted proteomics, such as selected reaction monitoring (SRM) and parallel reaction monitoring (PRM), have greatly improved the accuracy and reliability of phosphoprotein quantification. This quantitative data can be used to build mathematical models of phospho-signaling pathways, providing valuable insights for better diagnosis and treatment of diseases.
Review
Biochemistry & Molecular Biology
Duangnapa Kovanich, Teck Yew Low, Manuela Zaccolo
Summary: cAMP is a second messenger that plays a crucial role in regulating cellular functions. The compartmentalization of cAMP signaling is essential for its specificity, and the formation of dynamic signaling domains is responsible for precise spatiotemporal regulation. Proteomics can be used to identify the components of these domains and define the dynamic landscape of cellular cAMP signaling. Understanding compartmentalized cAMP signaling in physiological and pathological conditions can provide insights into disease mechanisms and guide the development of precision medicine interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Pey Yee Lee, Yeelon Yeoh, Teck Yew Low
Summary: Kinases play important roles in regulating biological processes and are associated with cancer. Small-molecule kinase inhibitors have revolutionized cancer treatment, but their selectivity and effectiveness are still challenging. This review provides an overview of the role of kinases in carcinogenesis, the progress of approved small-molecule kinase inhibitors, and the application of mass spectrometry-based proteomics strategies in kinase inhibitor design. It also discusses the challenges and outlook of mass spectrometry-based proteomics techniques for kinase drug research.
Article
Cell Biology
Him Shrestha, Tao Yao, Zhenzhen Qiao, Wellington Muchero, Robert L. L. Hettich, Jin-Gui Chen, Paul E. E. Abraham
Summary: PtLecRLK1 acts as a susceptibility factor in facilitating root colonization by Laccaria bicolor. It modifies multiple signaling pathways including plant defense, MAPK signaling, phytohormone signaling, ROS balance, endocytosis, cytoskeleton movement, and proteasomal degradation to establish and maintain L. bicolor colonization. Additionally, a cGMP-dependent protein kinase may be implicated as a substrate of PtLecRLK1.
Article
Physiology
Isabella Cattani-Cavalieri, Yue Li, Jordyn Margolis, Amy Bogard, Moom R. Roosan, Rennolds S. Ostrom
Summary: Human airway smooth muscle (HASM) is the primary target of ssAR agonists used to control airway hypercontractility in asthma and COPD. Different GPCR in HASM cells transduce extracellular signals through cAMP but elicit different cellular responses. This study used quantitative phosphoproteomics to define the downstream signaling networks resulting from cAMP produced by two adenylyl cyclases isoforms with contrasting localization in human airway smooth muscle.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Virology
Andrew P. P. Kurland, Boris Bonaventure, Jeffrey R. R. Johnson
Summary: In this study, we identified kinases that regulate innate immune pathways by conducting a small-scale kinase inhibitor screen and quantitative proteomics analysis. We found that inhibitors of ATM, ATR, AMPK, and PLK1 reduced interferon-stimulated gene expression in response to poly(I:C)-induced activation of innate immune pathways. However, RNA interference experiments did not validate these findings, suggesting off-target effects of the inhibitors. Mapping the effects of kinase inhibitors on various stages of innate immune pathways may reveal novel mechanisms of pathway control.
Article
Biochemical Research Methods
Soumya Mukherjee, Andris Jankevics, Florian Busch, Markus Lubeck, Yang Zou, Gary Kruppa, Albert J. R. Heck, Richard A. Scheltema, Karli R. Reiding
Summary: Ion mobility enables spatial separation of ions in the gas phase, providing information about their size. The timsTOF Pro device can physically separate N-glycopeptides from nonmodified peptides and produce high-quality fragmentation spectra. This method allows for the effective selection of analytes of interest based on the clear cluster in the mobiologram formed by the glycan moieties enlarging the size of glycopeptides.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Biochemical Research Methods
Wouter van Bergen, Johannes F. Hevler, Wei Wu, Marc P. Baggelaar, Albert J. R. Heck
Summary: Most drugs target proteins, and determining the exact drug binding sites on proteins is crucial for understanding their effects. A strategy called PhosID-ABPP was developed to identify drug binding sites using immobilized metal-affinity chromatography and phosphonate affinity tags. This method successfully identified over 500 unique binding sites of the drug PF-06672131. PhosID-ABPP also revealed differences in binding sites between intact cells and cell lysates, and captured a previously elusive binding site on the epidermal growth factor receptor.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Review
Chemistry, Multidisciplinary
Evolene Desligniere, Amber Rolland, Eduard H. T. M. Ebberink, Victor Yin, Albert J. R. Heck
Summary: Native mass spectrometry is widely used for determining the mass of intact proteins and their biomolecular assemblies. However, it can be challenging for heterogeneous protein complexes. In 2012, an Orbitrap-based mass analyzer with extended mass range was introduced, enabling high-resolution mass spectra of large protein assemblies and single ion measurements. This led to the development of single-molecule Orbitrap-based charge detection mass spectrometry in 2020, which has opened doors for innovative research in various systems.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Gunasekaran Subramaniam, Katharina Schleicher, Duangnapa Kovanich, Anna Zerio, Milda Folkmanaite, Ying-Chi Chao, Nicoletta C. Surdo, Andreas Koschinski, Jianshu Hu, Arjen Scholten, Albert J. R. Heck, Maria Ercu, Anastasiia Sholokh, Kyung Chan Park, Enno Klussmann, Viviana Meraviglia, Milena Bellin, Sara Zanivan, Svenja Hester, Shabaz Mohammed, Manuela Zaccolo
Summary: In this study, previously unrecognized cAMP nanodomains associated with beta-adrenergic stimulation were identified using an integrated phosphoproteomics approach and network analysis. The composition and function of one of these nanodomains were validated. The findings reveal a mechanism that explains the negative long-term clinical outcome observed in patients with heart failure treated with PDE3 inhibitors.
CIRCULATION RESEARCH
(2023)
Article
Biochemical Research Methods
Shelley Jager, Dario A. T. Cramer, Albert J. R. Heck
Summary: Alpha-1-antitrypsin (A1AT) has been suggested as a potential biomarker for distinguishing healthy and diseased individuals. However, the variability of the SERPINA1 gene in the general population may affect A1AT expression and serum protein levels, which are often overlooked in proteomics studies. This study found significant differences in allele-specific protein serum levels of A1AT among heterozygous donors, suggesting the importance of considering these factors when analyzing A1AT as a potential serum biomarker.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Johannes F. Hevler, Pascal Albanese, Alfredo Cabrera-Orefice, Alisa Potter, Andris Jankevics, Jelena Misic, Richard A. Scheltema, Ulrich Brandt, Susanne Arnold, Albert J. R. Heck
Summary: The tricarboxylic acid cycle is a central pathway for energy production in eukaryotic cells and plays a key role in aerobic respiration across all life kingdoms. The 2-oxoglutarate dehydrogenase complex (OGDHC) is a crucial enzyme in this cycle, generating NADH by oxidatively decarboxylating 2-oxoglutarate to succinyl-CoA. We provide evidence that MRPS36 is an important component of eukaryotic OGDHC, supported by cross-linking mass spectrometry data and phylogenetic analyses. We propose that MRPS36 evolved as an E3 adaptor protein, functionally replacing the peripheral subunit-binding domain (PSBD) in eukaryotic E2o.
Article
Andrology
Min Zhang, Riccardo Zenezini Chiozzi, Elizabeth G. Bromfield, Albert J. R. Heck, J. Bernd Helms, Bart M. Gadella
Summary: This study aimed to identify the interacting partners of CRISP2. The interactions of these binding partners were investigated under different conditions. The results suggest that CRISP2 may act as a scaffold for protein complex formation and dissociation to ensure the correct positioning of proteins required for the acrosome reaction and zona pellucida penetration.
Article
Biology
Leire Aguinagalde Salazar, Maurits A. den Boer, Suzanne M. Castenmiller, Seline A. Zwarthoff, Carla de Haas, Piet C. Aerts, Frank J. Beurskens, Janine Schuurman, Albert J. R. Heck, Kok van Kessel, Suzan H. M. Rooijakkers
Summary: In this study, it is found that by modifying the structure of monoclonal antibodies (mAbs), the immune protection and bactericidal effect against Streptococcus pneumoniae can be improved. The modified mAbs effectively activate the complement system and recruit complement component C1 for bacterial clearance, enhancing the antibacterial activity against various serotypes of pneumococci. This study provides an important proof of concept for the future development of antibody therapies against encapsulated bacteria.
Article
Biotechnology & Applied Microbiology
Yen-Hsi Chen, Weihua Tian, Makiko Yasuda, Zilu Ye, Ming Song, Ulla Mandel, Claus Kristensen, Lorenzo Povolo, Andre R. A. Marques, Tomislav Caval, Albert J. R. Heck, Julio Lopes Sampaio, Ludger Johannes, Takahiro Tsukimura, Robert Desnick, Sergey Y. Y. Vakhrushev, Zhang Yang, Henrik Clausen
Summary: Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due to short circulation times and suboptimal biodistribution of the therapeutic enzymes. Researchers have engineered Chinese hamster ovary (CHO) cells to produce glycoengineered enzymes, which have improved circulation time and biodistribution. This glycoengineering approach, known as Long-Acting-GlycoDesign (LAGD), may be widely applicable to lysosomal replacement enzymes to improve their circulatory stability and therapeutic efficacy.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Oncology
Beiping Miao, Zhaoqing Hu, Riccardo Mezzadra, Lotte Hoeijmakers, Astrid Fauster, Shangce Du, Zhi Yang, Melanie Sator-Schmitt, Helena Engel, Xueshen Li, Caroline Broderick, Guangzhi Jin, Raquel Gomez-Eerland, Lisette Rozeman, Xin Lei, Hitoshi Matsuo, Chen Yang, Ingrid Hofland, Dennis Peters, Annegien Broeks, Elke Laport, Annika Fitz, Xiyue Zhao, Mohamed A. A. Mahmoud, Xiujian Ma, Sandrine Sander, Hai-kun Liu, Guoliang Cui, Yu Gan, Wei Wu, Yanling Xiao, Albert J. R. Heck, Wenxian Guan, Scott W. Lowe, Hugo M. Horlings, Cun Wang, Thijn R. Brummelkamp, Christian U. Blank, Ton N. M. Schumacher, Chong Sun
Summary: The dysregulation of immune checkpoint molecules allows cancer cells to escape immune destruction. CD58, an important costimulatory ligand, is found to be positively regulated by CMTM6, which also interacts with PD-L1. The presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and the response to PD-L1-PD-1 blockade.
Article
Cell Biology
Dusanka Milenkovic, Jelena Misic, Johannes F. Hevler, Thibaut Molinie, Injae Chung, Ilian Atanassov, Xinping Li, Roberta Filograna, Andrea Mesaros, Arnaud Mourier, Albert J. R. Heck, Judy Hirst, Nils-Goran Larsson
Summary: The mammalian respiratory chain complexes CI, CIII2, and CIV form a stable assembly called the respirasome, which is critical for cellular bioenergetics. By studying knockin mice with decreased levels of respirasomes, researchers found that high levels of respirasomes are dispensable for maintaining bioenergetics and physiology in mice. However, the alternate functions of respirasomes, such as regulating protein stability and preventing age-associated protein aggregation, need further investigation.
Article
Biochemical Research Methods
Johannes F. Hevler, Albert J. R. Heck
Summary: Mitochondria, packed with proteins, play important roles in various cellular processes. While many mitochondrial protein complexes have been identified, some protein-protein interactions remain elusive. Cross-linking mass spectrometry (XL-MS) has proven to be a valuable tool for the in-depth characterization of these interactions. In this article, experimental strategies for the analysis of proteome-wide protein-protein interactions in mitochondria using XL-MS are highlighted, along with recent technological advances that can further enhance the in situ characterization of these interactions.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Oncology
Marjolein C. Stip, Mitchell Evers, Maaike Nederend, Chilam Chan, Karli R. Reiding, Mirjam J. Damen, Albert J. R. Heck, Sofia Koustoulidou, Ruud Ramakers, Gerard C. Krijger, Remmert de Roos, Edouard Souteyrand, Annelisa M. Cornel, Miranda P. Dierselhuis, Marco Jansen, Mark de Boer, Thomas Valerius, Geert van Tetering, Jeanette H. W. Leusen, Friederike Meyer-Wentrup
Summary: Researchers engineered an antibody called IgA3.0 ch14.18, which shows promise as a new therapy for neuroblastoma. The antibody has a longer half-life, increased protein stability, and potent tumor-killing abilities.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Inge Gazi, Karli R. Reiding, Andre Groeneveld, Jan Bastiaans, Thom Huppertz, Albert J. R. Heck
Summary: We monitored the changes in bovine milk IgG over a 28-day period after calving, finding that IgG accounts for over 50% of protein content in colostrum but less than 3% in mature milk. The N-glycosylation profile of bovine milk IgG was found to be highly heterogeneous with over 40 glycoforms, and this profile changed significantly during lactation. We also identified the presence of IgG3 subtype in bovine milk, alongside IgG1 and IgG2. These findings are important for understanding calf's immune development and the nutritional value of bovine milk.
Article
Immunology
Kelly A. Dingess, Max Hoek, Danique M. H. van Rijswijk, Sem Tamara, Maurits A. den Boer, Tim Veth, Mirjam J. A. Damen, Arjan Barendregt, Michelle Romijn, Hannah G. Juncker, Britt J. van Keulen, Gestur Vidarsson, Johannes B. van Goudoever, Albert Bondt, Albert J. R. Heck
Summary: The most abundant immunoglobulin in the human body is IgA and it is found in high concentrations in mucosal lining and biofluids like milk. The structure and clonal repertoire of IgA1-containing molecular assemblies were analyzed using mass spectrometry-based approach in serum and milk from three donors. The results showed that serum IgA1 consists of two distinct structural populations, monomeric IgA1 and dimeric J-chain coupled IgA1, while IgA1 in milk is present only as secretory IgA (SIgA) with various assemblies. The IgA1-Fab repertoires in serum and milk were also found to be different.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)