Review
Biochemistry & Molecular Biology
Emma Marie Wilber Hepworth, Shanta D. Hinton
Summary: MAPK signaling pathways are crucial regulators of eukaryotic cell function, with kinases and phosphatases controlling the activation and inhibition of MAPK. Pseudoenzymes also play a significant role in regulating these pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Malathi Bheri, Swati Mahiwal, Sibaji K. Sanyal, Girdhar K. Pandey
Summary: Protein phosphorylation and dephosphorylation are important reversible post-translational modifications, with protein phosphatases playing a key role in signaling networks. The classification and mechanism of phosphatases in plant systems still require further investigation.
Article
Psychiatry
S. Dominguez-Alonso, A. Carracedo, C. Rodriguez-Fontenla
Summary: Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders characterized by difficulties in social interaction and communication. The study uses a newly developed tool called eQTpLot to analyze the largest ASD GWAS data, along with GWAS summary statistics from other studies, to identify genes associated with ASD.
TRANSLATIONAL PSYCHIATRY
(2023)
Review
Public, Environmental & Occupational Health
Deqiang Liu, Yiming Zhang, Hui Fang, Jinxiang Yuan, Lizhen Ji
Summary: Pseudophosphatases are a class of enzymes that mutate at the catalytically active site and play important roles in life processes and diseases. This review discusses the structures, action types, and signaling mechanisms of pseudophosphatases in various families.
FRONTIERS IN PUBLIC HEALTH
(2022)
Review
Biochemistry & Molecular Biology
Julio Sevillano, Maria Gracia Sanchez-Alonso, Javier Pizarro-Delgado, Maria del Pilar Ramos-Alvarez
Summary: Changes in lifestyle in developed countries have led to the prevalence of obesity and type 2 diabetes mellitus. Identifying potential therapeutic targets and early biomarkers is crucial in addressing these metabolic diseases. The role of protein tyrosine phosphatases in insulin signaling cascade and secretion is significant in metabolic diseases like obesity and T2DM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Andrew M. Mattei, Jonathan D. Smailys, Emma Marie Wilber Hepworth, Shanta D. Hinton
Summary: Pseudophosphatases, atypical members of the protein tyrosine phosphatase family, play important roles in physiology and pathophysiology as key regulators in signaling cascades. By investigating their involvement in diseases and pathologies, pseudophosphatases have emerged as potential therapeutic drug targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Shanelle R. Shillingford, Anton M. Bennett
Summary: Phosphatases and kinases play crucial roles in maintaining the balance between dephosphorylated and phosphorylated proteins for cellular functions. Imbalance or dysfunction in their activities can lead to unfavorable cellular effects and the development of diseases. Protein tyrosine phosphatases (PTPs) are attractive therapeutic targets due to their involvement in cell signaling and diseases, but they have been challenging in drug development. This article focuses on the progress in small-molecule inhibition of the mitogen-activated protein kinase (MAPK) phosphatases (MKPs), discussing successful strategies and inhibitor discovery tools, as well as the potential future of MKP inhibition.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Rory M. Crean, Michal Biler, Marc W. van der Kamp, Alvan C. Hengge, Shina C. L. Kamerlin
Summary: This study investigates the link between the dynamics of the WPD-loop and catalysis rates in human protein tyrosine phosphatase 1B (PTP1B) and YopH from Yersinia pestis. Computational simulations reveal key residues and structural features responsible for differences in loop dynamics, as well as pathways for allosteric communication in these enzymes. The findings shed light on how PTP enzymes in the family may adapt to environmental changes and regulate their catalytic activities.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Neurosciences
Noopur Bhore, Bo-Jeng Wang, Po-Fan Wu, Yen-Lurk Lee, Yun-Wen Chen, Wen-Ming Hsu, Hsinyu Lee, Yi-Shuian Huang, Ding- Yang, Yung-Feng Liao
Summary: Research showed that DUSP15 can affect Notch processing by regulating ERK1/2 activity to influence Notch protein levels, revealing a novel signaling axis.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemical Research Methods
Anna Serbina, Anthony C. Bishop
Summary: This study demonstrates the use of differential scanning fluorimetry as a rapid and quantitative method to measure the strength of SHP2 autoinhibition. This method does not require protein labeling or specialized instrumentation and is applicable for evaluating the autoinhibitory interactions in different SHP2 mutants.
ANALYTICAL BIOCHEMISTRY
(2023)
Article
Plant Sciences
Fei-Hua Yao, Xiao Liang, Xin-Hua Lu, Xia Cheng, Lian-Xiang Luo, Shu-Hua Qi
Summary: Seven new decahydrofluorene-class alkaloids, pyrrospirones K-Q (1-7), were isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41512. Compound 13 exhibited significant inhibitory activity against protein tyrosine phosphatases. Moreover, compounds 1, 2, 5, 8-10, 12, and 13 showed antibacterial activity.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Psychiatry
Christie L. Burton, Mathieu Lemire, Bowei Xiao, Elizabeth C. Corfield, Lauren Erdman, Janita Bralten, Geert Poelmans, Dongmei Yu, S-M Shaheen, Tara Goodale, Vanessa M. Sinopoli, Noam Soreni, Gregory L. Hanna, Kate D. Fitzgerald, David Rosenberg, Gerald Nestadt, Andrew D. Paterson, Lisa J. Strug, Russell J. Schachar, Jennifer Crosbie, Paul D. Arnold
Summary: The study investigated genetic variants associated with obsessive-compulsive (OC) traits and found shared genetic risk between OC traits and obsessive-compulsive disorder (OCD). The research identified a significant genetic variant for OC traits and demonstrated the feasibility of using trait-based approaches for genetic discovery in community samples.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Alessandra V. S. Faria, Bingting Yu, Michiel Mommersteeg, Patricia F. de Souza-Oliveira, Sheila S. Andrade, Manon C. W. Spaander, Moniek P. M. de Maat, Maikel P. Peppelenbosch, Carmen Ferreira-Halder, Gwenny M. Fuhler
Summary: LMWPTP, a member of the protein tyrosine phosphatase family, has been found to be overexpressed in cancer cells and to promote tumor cell proliferation through interaction with platelets. These findings suggest that LMWPTP may play a key role in driving oncogenic changes in tumor cells by enhancing their interaction with platelets.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Evan T. Liechty, Andrew Hren, Levi Kramer, Gregory Donovan, Anika J. Friedman, Michael R. Shirts, Jerome M. Fox
Summary: Neutral mutational drift is an important but underutilized source of biological diversity in protein biophysics. This study focuses on protein tyrosine phosphatase 1B (PTP1B) and investigates how neutral drift impacts its catalytic activity and stability. The findings suggest that neutral or mildly activating mutations can counteract deleterious ones, indicating a moderate activity-stability tradeoff. The study also shows that neutral mutations in allosterically influential sites are purged under biological selection, enriching for mutations outside of the active site.
Article
Biochemistry & Molecular Biology
Valerie Vinette, Isabelle Aubry, Hayley Insull, Noriko Uetani, Serge Hardy, Michel L. Tremblay
Summary: Metabolic reprogramming in cancer cells is regulated by tyrosine kinases and tyrosine phosphatases. Among the protein tyrosine phosphatase (PTP) superfamily, TC-PTP (PTPN2) has been identified as a key regulator of mitochondrial metabolism in cancer cells, with its inhibition resulting in functional defects in oxidative metabolism.
Article
Genetics & Heredity
Karen W. Gripp, Lisa Schill, Lisa Schoyer, Beth Stronach, Anton M. Bennett, Susan Blaser, Amanda Brown, Rebecca Burdine, Emma Burkitt-Wright, Pau Castel, Sandra Darilek, Alwyn Dias, Tuesdi Dyer, Michelle Ellis, Gregg Erickson, Bruce D. Gelb, Tamar Green, Andrea Gross, Alan Ho, James Lloyd Holder, Shin-Ichi Inoue, Angie C. Jelin, Annie Kennedy, Richard Klein, Maria I. Kontaridis, Pilar Magoulas, Darryl B. McConnell, Frank McCormick, Benjamin G. Neel, Carlos E. Prada, Katherine A. Rauen, Amy Roberts, Pablo Rodriguez-Viciana, Neal Rosen, Gavin Rumbaugh, Anna Sablina, Maja Solman, Marco Tartaglia, Angelica Thomas, William C. Timmer, Kartik Venkatachalam, Karin S. Walsh, Pamela L. Wolters, Jae-Sung Yi, Martin Zenker, Nancy Ratner
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2020)
Article
Medicine, Research & Experimental
Jae-Sung Yi, Sravan Perla, Liz Enyenihi, Anton M. Bennett
Article
Biochemistry & Molecular Biology
Zachary T. K. Gannam, Kisuk Min, Shanelle R. Shillingford, Lei Zhang, James Herrington, Laura Abriola, Peter C. Gareiss, Georgios Pantouris, Argyrios Tzouvelekis, Naftali Kaminski, Xinbo Zhang, Jun Yu, Haya Jamali, Jonathan A. Ellman, Elias Lolis, Karen S. Anderson, Anton M. Bennett
Article
Cardiac & Cardiovascular Systems
Jae-Sung Yi, Sravan Perla, Yan Huang, Kana Mizuno, Frank J. Giordano, Alexander A. Vinks, Anton M. Bennett
Summary: Low-dose dasatinib showed linear pharmacokinetic properties in NSML mice, with exposure-dependent inhibition of c-Src and PZR tyrosyl phosphorylation as well as AKT phosphorylation. A dose as low as 0.1 mg/kg of dasatinib prevented HCM in NSML mice and transcriptome analysis identified reversal of HCM-associated gene expression levels in the heart tissue.
CARDIOVASCULAR DRUGS AND THERAPY
(2022)
Review
Cardiac & Cardiovascular Systems
Jae-Sung Yi, Sravan Perla, Anton M. Bennett
Summary: Mutations in the RAS/mitogen-activated protein kinase (MAPK) pathway cause a group of developmental diseases known as RASopathies. These diseases are characterized by a wide range of congenital heart defects, and targeted therapies for RASopathy-associated HCM have shown promise. However, safety and risk assessment in treating children remain crucial considerations.
CARDIOVASCULAR DRUGS AND THERAPY
(2022)
Article
Immunology
Chao Zhong, Kisuk Min, Zhiqiang Zhao, Cheng Zhang, Erhe Gao, Yan Huang, Xinbo Zhang, Margaret Baldini, Rajika Roy, Xiaofeng Yang, Walter J. Koch, Anton M. Bennett, Jun Yu
Summary: Cardiac fibrosis, a pathological condition associated with excessive ECM deposition in the myocardium, is regulated by processes not fully understood. Macrophage-specific MKP-5 was found to modulate pressure overload-induced cardiac fibrosis, with its deficiency resulting in upregulation of ECM-degrading MMP-9 expression in Ly6C(low) cardiac macrophages. This study indicates that MKP-5 may play a role in suppressing ECM-degrading activity through MAPK-mediated regulation of MMP-9 expression in cardiac macrophages.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Maria Kontaridis, Amy E. Roberts, Lisa Schill, Lisa Schoyer, Beth Stronach, Gregor Andelfinger, Yoko Aoki, Marni E. Axelrad, Annette Bakker, Anton M. Bennett, Alberto Broniscer, Pau Castel, Caitlin A. Chang, Lukas Cyganek, Tirtha K. Das, Jeroen den Hertog, Emilia Galperin, Shruti Garg, Bruce D. Gelb, Kristiana Gordon, Tamar Green, Karen W. Gripp, Maxim Itkin, Maija Kiuru, Bruce R. Korf, Jeff R. Livingstone, Alejandro Lopez-Juarez, Pilar L. Magoulas, Sahar Mansour, Theresa Milner, Elisabeth Parker, Elizabeth Pierpont, Kevin Plouffe, Katherine A. Rauen, Suma P. Shankar, Shane B. Smith, David A. Stevenson, Marco Tartaglia, Richard Van, Morgan E. Wagner, Stephanie M. Ware, Martin Zenker
Summary: RASopathies are a group of genetic disorders caused by genes affecting the Ras/MAPK signaling pathway. Progress has been made in translating research findings to the clinic, with the use of pathway inhibitors for treatment. The seventh International RASopathies Symposium aimed to enhance new discoveries in the field and bring together stakeholders from various backgrounds.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Review
Pharmacology & Pharmacy
Shanelle R. Shillingford, Anton M. Bennett
Summary: Phosphatases and kinases play crucial roles in maintaining the balance between dephosphorylated and phosphorylated proteins for cellular functions. Imbalance or dysfunction in their activities can lead to unfavorable cellular effects and the development of diseases. Protein tyrosine phosphatases (PTPs) are attractive therapeutic targets due to their involvement in cell signaling and diseases, but they have been challenging in drug development. This article focuses on the progress in small-molecule inhibition of the mitogen-activated protein kinase (MAPK) phosphatases (MKPs), discussing successful strategies and inhibitor discovery tools, as well as the potential future of MKP inhibition.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Article
Chemistry, Medicinal
Zira T. K. Gannam, Haya Jamali, Oh Sang Kweon, James Herrington, Shanelle R. Shillingford, Christina Papini, Erik Gentzel, Elias Lolis, Anton M. Bennett, Jonathan A. Ellman, Karen S. Anderson
Summary: This study explores the structure-activity relationship of a class of MKP5 inhibitors and designs and synthesizes a series of derivative compounds for evaluation of MKP5 inhibition. The crystal structures of enzyme-inhibitor complexes are further analyzed to elucidate the necessary requirements for MKP5 inhibition. The results lay the foundation for the development of more potent MKP5 allosteric inhibitors for the treatment of dystrophic muscle disease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Anton M. Bennett
Summary: The identification of substrates for protein tyrosine phosphatases (PTPs) is crucial for understanding their function. In a recent study, Bonham et al. developed a modified method combining substrate-trapping mutations with proximity-labeling mass spectrometry (MS) to identify the protein substrates and interactors of PTP1B. This method revealed interaction networks in breast cancer cell models and discovered novel targets of PTP1B that regulate HER2 signaling pathways. This strategy represents a versatile new tool for identifying the functional interactions between PTPs and their substrates.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Medicine, General & Internal
Theodoros Karampitsakos, Apostolos Galaris, Ilianna Barbayianni, Giuseppe DeIuliis, Farida Ahangari, Fotis Sampsonas, Vasilina Sotiropoulou, Vassilis Aidinis, Anton M. Bennett, Jose D. Herazo-Maya, Nikolaos Xylourgidis, Petros Bakakos, Demosthenes Bouros, Naftali Kaminski, Argyrios Tzouvelekis
Summary: SHP2 downregulation may predispose fibroblasts to differentiate into myofibroblasts and play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Recent data have shown that SHP2 localizes to the mitochondrial intercristae, and its overexpression enhances mitochondrial metabolism leading to oxidative stress and senescence. Through a series of experiments, it was found that SHP2 attenuates fibrotic responses by negatively regulating mitochondrial metabolism and inducing autophagy.
Meeting Abstract
Biochemistry & Molecular Biology
Anton Bennett
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Meeting Abstract
Hematology
Xinbo Zhang, Zhiqiang Zhao, Margaret Baldini, Cheng Zhang, Bo Tao, Lei Zhang, Anton M. Bennett, Jun Yu
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Meeting Abstract
Sport Sciences
Kisuk Min Min, Yan Huang, Anton Bennett
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Kisuk Min, Yan Huang, Frank J. Giordano, Sudip Bajpeyi, Anton M. Bennett