18,584 results match your criteria pi45p dephosphorylation

Phosphorylated LASS2 inhibits prostate carcinogenesis via negative regulation of Wnt/β-catenin signaling.

J Cell Biochem 2021 Apr 14. Epub 2021 Apr 14.

Department of Pathology, Peking University Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

LASS2 is a novel tumor-suppressor gene and has been characterized as a ceramide synthase, which synthesizes very-long acyl chain ceramides. However, LASS2 function and pathway-related activity in prostate carcinogenesis are still largely unexplored. Here, we firstly report that LASS2 promotes β-catenin degradation through physical interaction with STK38, SCYL2, and ATP6V0C via the ubiquitin-proteasome pathway, phosphorylation of LASS2 is essential for β-catenin degradation, and serine residue 248 of LASS2 is illustrated to be a key phosphorylation site. Read More

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Genome-wide survey of tyrosine phosphatases in thirty mammalian genomes.

Cell Signal 2021 Apr 10:110009. Epub 2021 Apr 10.

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore, Karnataka, 560 065, India. Electronic address:

The age of genomics has given us a wealth of information and the tools to study whole genomes. This, in turn, has facilitated genome-wide studies among organisms that were relatively less studied in the pre-genomic era or are non-model organisms. This paves the way to the discovery of interesting evolutionary patterns, which are brought to light by genome-wide surveys of protein superfamilies. Read More

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SEPT6 drives hepatocellular carcinoma cell proliferation, migration and invasion via the Hippo/YAP signaling pathway.

Int J Oncol 2021 Jun 13;58(6). Epub 2021 Apr 13.

Department of Medicine II, Liver Center Munich, University Hospital, Ludwig‑Maximilians‑University of Munich, Munich 81377, Germany.

Septin 6 (SEPT6) is a member of the GTP‑binding protein family that is highly conserved in eukaryotes and regulates various biological functions, including filament dynamics, cytokinesis and cell migration. However, the functional importance of SEPT6 in hepatocellular carcinoma (HCC) is not completely understood. The present study aimed to investigate the expression levels and roles of SEPT6 in HCC, as well as the underlying mechanisms. Read More

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Structure, Function and Modulation of Striatal-enriched Protein Tyrosine Phosphatase (STEP).

Curr Med Chem 2021 Apr 12. Epub 2021 Apr 12.

Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Science, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong 250012. China.

Striatal-enriched protein tyrosine phosphatase (STEP) is exclusively expressed in the central nervous system and regulates various neuronal signaling factors through the dephosphorylation of different substrates. Dysregulated expression or uncontrollable enzymatic activity of STEP contributes to neurological disorders such as Alzheimer's disease, which makes it a promising pharmaceutical target. Herein, we reviewed the structure and biological functions of STEP, as well as the recent development of small- molecule STEP modulators. Read More

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The lectin Orysata induces phosphatase-mediated and carbohydrate-independent aggregation of insect cells.

J Insect Physiol 2021 Apr 9:104241. Epub 2021 Apr 9.

Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium.

Lectins, or carbohydrate-binding proteins, can cause agglutination of particular cells. This process is mediated by the interaction of the carbohydrate-binding domain with sugar structures on the cell surface, and this binding can be inhibited by pre-incubation of the lectin with its specific sugars. However, when incubated with insect cells, Orysata, a mannose-binding lectin from rice, caused aggregation of the cells, independent from carbohydrate binding activity. Read More

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LncRNA MEG3 Alleviates Diabetic Cognitive Impairments by Reducing Mitochondrial-Derived Apoptosis through Promotion of FUNDC1-Related Mitophagy via Rac1-ROS Axis.

ACS Chem Neurosci 2021 Apr 12. Epub 2021 Apr 12.

Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China.

Mitochondrial dysfunction and elevated ROS generation are predominant contributors of neuronal death that is responsible for the diabetes-related cognitive impairments. Emerging evidence has demonstrated that long noncoding RNA-MEG3 can serve as an important regulator in the pathogenesis of diabetes. However, the underlying mechanisms remain to be further clarified. Read More

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Sustained IKKβ phosphorylation and NF-κB activation by superoxide-induced peroxynitrite-mediated nitrotyrosine modification of B56γ3 and PP2A inactivation.

Redox Biol 2020 Dec 18;41:101834. Epub 2020 Dec 18.

National University Cancer Institute, National University Health System, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, NUS, Singapore; Integrative Science and Engineering Programme, NUS Graduate School, NUS, Singapore; Faculté de Medicine, University of Paris, Paris, France. Electronic address:

Apart from its physiological role in inflammation and immunity, the nuclear factor-kappa B (NF-κB) protein complex has been implicated in tumorigenesis and its progression. Here, we provide evidence that a pro-oxidant milieu is an upstream effector of oncogenic NF-κB signaling. Through pharmacological or genetic inhibition of SOD1, we show that elevated intracellular superoxide (O) mediates sustained IKK phosphorylation, and induces downstream degradation of IκBα, leading to the nuclear localization and transcriptional activation of NF-κB. Read More

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December 2020

Genetic deletion of Nox4 enhances cancerogen-induced formation of solid tumors.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Institute for Cardiovascular Physiology, Goethe University, 60590 Frankfurt am Main, Germany;

Reactive oxygen species (ROS) can cause cellular damage and promote cancer development. Besides such harmful consequences of overproduction of ROS, all cells utilize ROS for signaling purposes and stabilization of cell homeostasis. In particular, the latter is supported by the NADPH oxidase 4 (Nox4) that constitutively produces low amounts of HO By that mechanism, Nox4 forces differentiation of cells and prevents inflammation. Read More

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Reevaluation of Phytase Action Mechanism in Animal Nutrition.

Biochemistry (Mosc) 2021 Jan;86(Suppl 1):S152-S165

Poultry Institute, Sergiev Posad, Moscow Region, 141311, Russia.

The release of phosphorus from phytates occurs via sequential cleavage of phosphate groups. It was believed that, regardless of the properties of phytases, the rate of phytate dephosphorylation is limited by the first cleavage of any phosphate group. The position of the first cleaved-off phosphate group depending on the specificity of phytase. Read More

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January 2021

Protein tyrosine phosphatase receptor type D gene promotes radiosensitivity via STAT3 dephosphorylation in nasopharyngeal carcinoma.

Oncogene 2021 Apr 6. Epub 2021 Apr 6.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Radiotherapy is essential to the treatment of nasopharyngeal carcinoma (NPC) and acquired or innate resistance to this therapeutic modality is a major clinical problem. However, the underlying molecular mechanisms in the radiation resistance in NPC are not fully understood. Here, we reanalyzed the microarray data from public databases and identified the protein tyrosine phosphatase receptor type D (PTPRD) as a candidate gene. Read More

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Targeting nucleotide metabolism enhances the efficacy of anthracyclines and anti-metabolites in triple-negative breast cancer.

NPJ Breast Cancer 2021 Apr 6;7(1):38. Epub 2021 Apr 6.

Medicine, Dentistry and Biomedical Sciences: Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.

Triple-negative breast cancer (TNBC) remains the most lethal breast cancer subtype with poor response rates to the current chemotherapies and a lack of additional effective treatment options. We have identified deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) as a critical gatekeeper that protects tumour DNA from the genotoxic misincorporation of uracil during treatment with standard chemotherapeutic agents commonly used in the FEC regimen. dUTPase catalyses the hydrolytic dephosphorylation of deoxyuridine triphosphate (dUTP) to deoxyuridine monophosphate (dUMP), providing dUMP for thymidylate synthase as part of the thymidylate biosynthesis pathway and maintaining low intracellular dUTP concentrations. Read More

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Calcineurin inhibitors suppress acute graft-vs-host disease via NFAT-independent inhibition of T cell receptor signaling.

J Clin Invest 2021 Apr 6. Epub 2021 Apr 6.

Laboratory of Immune Cell Biology, NIH, Bethesda, United States of America.

Inhibitors of calcineurin phosphatase activity (CNIs) such as cyclosporin A (CsA) are widely used to treat tissue transplant rejection and acute graft-versus-host disease (aGVHD), for which inhibition of NFAT-dependent gene expression is the mechanistic paradigm. We recently reported that CNIs inhibit TCR-proximal signaling by preventing calcineurin-mediated dephosphorylation of LckS59, an inhibitory modification, raising the possibility of another mechanism by which CNIs suppress immune responses. Here we utilized T cells from mice that express LckS59A, which cannot accept a phosphate at residue 59, to initiate aGVHD. Read More

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Coupling of Cdc20 inhibition and activation by BubR1.

J Cell Biol 2021 May;220(5)

Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Science, Copenhagen, Denmark.

Tight regulation of the APC/C-Cdc20 ubiquitin ligase that targets cyclin B1 for degradation is important for mitotic fidelity. The spindle assembly checkpoint (SAC) inhibits Cdc20 through the mitotic checkpoint complex (MCC). In addition, phosphorylation of Cdc20 by cyclin B1-Cdk1 independently inhibits APC/C-Cdc20 activation. Read More

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Dapsone Ameliorates Colitis through TLR4/NF-kB Pathway in TNBS Induced Colitis Model in Rat.

Arch Med Res 2021 Apr 1. Epub 2021 Apr 1.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 13145-784, Tehran, Iran. Electronic address:

Background: Crohn's disease (CD), a type of inflammatory bowel disease (IBD), emerges with severe gastrointestinal (GI) tract inflammation, sometimes known as hostile abdomen. Conventional treatment of CD has several limitations such as insufficient response to treatment, and intolerable side effects of drugs. In addition, the high cost of biologic drugs prevents patients from continuing their treatment. Read More

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Deficiency of Lipin2 Results in Enhanced NF-κB Signaling and Osteoclast Formation in RAW-D Murine Macrophages.

Int J Mol Sci 2021 Mar 12;22(6). Epub 2021 Mar 12.

Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.

Lipin2 is a phosphatidate phosphatase that plays critical roles in fat homeostasis. Alterations in , which encodes lipin2, cause the autoinflammatory bone disorder Majeed syndrome. Lipin2 limits lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Read More

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Anticancer Potential of Damnacanthal and Nordamnacanthal from Roots on T-lymphoblastic Leukemia Cells.

Molecules 2021 Mar 12;26(6). Epub 2021 Mar 12.

Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia.

Background: This study reports on the cytotoxic properties of nordamnacanthal and damnacanthal, isolated from roots of on T-lymphoblastic leukaemia (CEM-SS) cell lines.

Methods: MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out.

Results: Nordamnacanthal and damnacanthal at IC values of 1. Read More

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Nicotinamide Treatment Facilitates Mitochondrial Fission through Drp1 Activation Mediated by SIRT1-Induced Changes in Cellular Levels of cAMP and Ca.

Cells 2021 Mar 10;10(3). Epub 2021 Mar 10.

Department of Life Science, University of Seoul, Jeonnong-dong, Dongdaemun-gu, Seoul 02504, Korea.

Mitochondrial autophagy (or mitophagy) is essential for mitochondrial quality control, which is critical for cellular and organismal health by attenuating reactive oxygen species generation and maintaining bioenergy homeostasis. Previously, we showed that mitophagy is activated in human cells through SIRT1 activation upon treatment of nicotinamide (NAM). Further, mitochondria are maintained as short fragments in the treated cells. Read More

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Activation of AMPK inhibits Galectin-3-induced pulmonary artery smooth muscle cells proliferation by upregulating hippo signaling effector YAP.

Mol Cell Biochem 2021 Apr 2. Epub 2021 Apr 2.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.

Galectin-3(Gal-3) is an effective regulator in the pathological process of pulmonary arterial hypertension (PAH). However, the detailed mechanisms underlying Gal-3 contribution to PAH are not yet entirely clear. The aim of the present study was to explore these issues. Read More

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LHPP-Mediated Histidine Dephosphorylation Suppresses the Self-Renewal of Mouse Embryonic Stem Cells.

Front Cell Dev Biol 2021 16;9:638815. Epub 2021 Mar 16.

Institute of Stem Cell and Regenerative Medicine, School of Medicine, Xiamen University, Xiamen, China.

Self-renewal of embryonic stem cells (ESCs) is orchestrated by a vast number of genes at the transcriptional and translational levels. However, the molecular mechanisms of post-translational regulatory factors in ESC self-renewal remain unclear. Histidine phosphorylation, also known as hidden phosphorylation, cannot be detected by conventional experimental methods. Read More

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Modulation of Gene Expression in Actinobacteria by Translational Modification of Transcriptional Factors and Secondary Metabolite Biosynthetic Enzymes.

Front Microbiol 2021 16;12:630694. Epub 2021 Mar 16.

Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, Mexico.

Different types of post-translational modifications are present in bacteria that play essential roles in bacterial metabolism modulation. Nevertheless, limited information is available on these types of modifications in actinobacteria, particularly on their effects on secondary metabolite biosynthesis. Recently, phosphorylation, acetylation, or phosphopantetheneylation of transcriptional factors and key enzymes involved in secondary metabolite biosynthesis have been reported. Read More

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Regulation of HBV Replication by Cyclin Docking Motifs in Core Protein.

J Virol 2021 Mar 31. Epub 2021 Mar 31.

Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA

Hepatitis B virus (HBV) capsid or core protein (HBc) consists of an N-terminal domain (NTD) and C-terminal domain (CTD) connected by a short linker peptide. Dynamic phosphorylation and dephosphorylation of HBc regulate its multiple functions in capsid assembly and viral replication. The cellular cyclin-dependent kinase 2 (CDK2) plays a major role in HBc phosphorylation and furthermore, is incorporated into the viral capsid, accounting for most of the "endogenous kinase" activity associated with the capsid. Read More

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PKC98E Regulates Odorant Responses in .

J Neurosci 2021 Mar 29. Epub 2021 Mar 29.

Departments of Neuroscience

Drosophila odorant receptors (Ors) are ligand gated ion channels composed of a common receptor subunit ORCO (odorant receptor co-receptor) and one of 62 'tuning' receptor subunits that confer odorant specificity to olfactory neuron responses. Like other sensory systems studied to date, exposing Drosophila olfactory neurons to activating ligands results in reduced responses to subsequent exposures through a process called desensitization. We recently showed that phosphorylation of serine 289 on the common odorant receptor subunit ORCO is required for normal peak olfactory neuron responses. Read More

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PPP6C negatively regulates oncogenic ERK signaling through dephosphorylation of MEK.

Cell Rep 2021 Mar;34(13):108928

Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address:

Flux through the RAF-MEK-ERK protein kinase cascade is shaped by phosphatases acting on the core components of the pathway. Despite being an established drug target and a hub for crosstalk regulation, little is known about dephosphorylation of MEK, the central kinase within the cascade. Here, we identify PPP6C, a phosphatase frequently mutated or downregulated in melanoma, as a major MEK phosphatase in cells exhibiting oncogenic ERK pathway activation. Read More

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Direct uptake of sphingosine-1-phosphate (S1P) independent of phospholipid phosphatases.

J Biol Chem 2021 Mar 27:100605. Epub 2021 Mar 27.

Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan. Electronic address:

Sphingosine-1-phosphate (S1P) is a lipid mediator that is relatively abundant in plasma and plays an important role in the vascular and immune systems. To date, the only known mechanism for removing S1P from plasma has been dephosphorylation by phospholipid phosphatases (PLPPs) on the surface of cells in contact with the plasma. However, there remains a possibility that PLPP-independent dephosphorylation or direct S1P uptake into cells could occur. Read More

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Prevention of guanylyl cyclase-B dephosphorylation rescues achondroplastic dwarfism.

JCI Insight 2021 Mar 30. Epub 2021 Mar 30.

Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, United States of America.

Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) or inactivating mutations in guanylyl cyclase B (GC-B), also known as NPR-B or Npr2, cause short-limbed dwarfism. FGFR3 activation causes dephosphorylation and inactivation of GC-B, but the contribution of GC-B dephosphorylation to achondroplasia (ACH) is unknown. GC-B7E/7E mice that express a glutamate-substituted version of GC-B that cannot be inactivated by dephosphorylation were bred with mice expressing FGFR3-G380R, the most common human ACH mutation, to determine if GC-B dephosphorylation is required for ACH. Read More

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Enzymatic Assemblies of Thiophosphopeptides Instantly Target Golgi Apparatus and Selectively Kill Cancer Cells.

Angew Chem Int Ed Engl 2021 Mar 30. Epub 2021 Mar 30.

Brandeis University, Department of Chemistry, 415 South St, 02454, 2454, Waltham, UNITED STATES.

Golgi apparatus is emerging as a key signaling hub of cells and an important target for cancer therapy, but there are few approaches for targeting Golgi and selectively killing cancer cells. Here we show an unexpected result that changing an oxygen atom of the phosphoester bond in phosphopeptides by a sulfur atom enables instantly targeting Golgi apparatus (GA) and selectively killing cancer cells by enzymatic self-assembly. Specifically, conjugating cysteamine S-phosphate to the C-terminal of a self-assembling peptide generates a thiophosphopeptide. Read More

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Amino terminus of cardiac myosin binding protein-C regulates cardiac contractility.

J Mol Cell Cardiol 2021 Mar 26;156:33-44. Epub 2021 Mar 26.

Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL 60153, USA; Heart, Lung and Vascular Institute, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267, USA. Electronic address:

Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) regulates cardiac contraction through modulation of actomyosin interactions mediated by the protein's amino terminal (N')-region (C0-C2 domains, 358 amino acids). On the other hand, dephosphorylation of cMyBP-C during myocardial injury results in cleavage of the 271 amino acid C0-C1f region and subsequent contractile dysfunction. Yet, our current understanding of amino terminus region of cMyBP-C in the context of regulating thin and thick filament interactions is limited. Read More

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Cerebral Ischemia-Reperfusion Is Associated With Upregulation of Cofilin-1 in the Motor Cortex.

Front Cell Dev Biol 2021 11;9:634347. Epub 2021 Mar 11.

Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Cerebral ischemia is one of the leading causes of death. Reperfusion is a critical stage after thrombolysis or thrombectomy, accompanied by oxidative stress, excitotoxicity, neuroinflammation, and defects in synapse structure. The process is closely related to the dephosphorylation of actin-binding proteins (e. Read More

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Nucleophosmin Protein Dephosphorylation by DUSP3 Is a Fine-Tuning Regulator of p53 Signaling to Maintain Genomic Stability.

Front Cell Dev Biol 2021 11;9:624933. Epub 2021 Mar 11.

Laboratory of Biomolecular Systems Signalling, Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.

The dual-specificity phosphatase 3 (DUSP3), an atypical protein tyrosine phosphatase (PTP), regulates cell cycle checkpoints and DNA repair pathways under conditions of genotoxic stress. DUSP3 interacts with the nucleophosmin protein (NPM) in the cell nucleus after UV-radiation, implying a potential role for this interaction in mechanisms of genomic stability. Here, we show a high-affinity binding between DUSP3-NPM and NPM tyrosine phosphorylation after UV stress, which is increased in DUSP3 knockdown cells. Read More

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Derrone Inhibits Platelet Aggregation, Granule Secretion, Thromboxane A Generation, and Clot Retraction: An Study.

Evid Based Complement Alternat Med 2021 10;2021:8855980. Epub 2021 Mar 10.

Department of Biomedical Laboratory Science, Far East University, Eumseong 27601, Republic of Korea.

() is widespread throughout East Asia and in China and Korea, and it is widely used as a traditional remedy against eczema, mumps, and tuberculosis. With regard to the aforementioned medical efficacy, various studies are continuously being conducted, and it has been reported that extract has various actions against inflammation, diabetes, obesity, and tumors. Therefore, we evaluated antiplatelet effects using derrone in We examined the effect of derrone on the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and inositol 1, 4, 5-triphosphate receptor I (IPRI), and on the dephosphorylation of cytosolic phospholipase A (cPLA), mitogen-activated protein kinases p38 (p38), and Akt, which affects platelet function and thrombus formation. Read More

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