35,996 results match your criteria phosphorylation sites


The CaM1-Associated CCaMK-MKK1/6 cascade positively affects the lateral root growth through auxin signaling under salt stress in rice.

J Exp Bot 2021 Jun 15. Epub 2021 Jun 15.

MOA Key Laboratory of Crop Ecophysiology and Farming System in the Middle Reaches of the Yangtze River, Huazhong Agricultural University, Wuhan, China.

CCaMKs and MAPKKs are two kinases that regulate salt stress response in plants. It remains unclear, however, how they cooperatively affect the lateral root growth under salt stress. Here, two conserved phosphorylation sites (S102 and T118) of OsCaM1 were identified, and affected the capability of binding to Ca 2+  in vitro and kinase activity of OsCCaMK in vivo. Read More

View Article and Full-Text PDF

Phosphorylation of meprin β controls its cell surface abundance and subsequently diminishes ectodomain shedding.

FASEB J 2021 Jul;35(7):e21677

Biochemical Institute, Unit for Degradomics of the Protease Web, University of Kiel, Kiel, Germany.

Meprin β is a zinc-dependent metalloprotease exhibiting a unique cleavage specificity with strong preference for acidic amino acids at the cleavage site. Proteomic studies revealed a diverse substrate pool of meprin β including the interleukin-6 receptor (IL-6R) and the amyloid precursor protein (APP). Dysregulation of meprin β is often associated with pathological conditions such as chronic inflammation, fibrosis, or Alzheimer's disease (AD). Read More

View Article and Full-Text PDF

Molecular and Clinical Characterization of UBE2S in Glioma as a Biomarker for Poor Prognosis and Resistance to Chemo-Radiotherapy.

Front Oncol 2021 27;11:640910. Epub 2021 May 27.

Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Glioblastoma is the most common and lethal brain cancer globally. Clinically, this cancer has heterogenous molecular and clinical characteristics. Studies have shown that UBE2S is highly expressed in many cancers. Read More

View Article and Full-Text PDF

Phosphoproteomic identification of ULK substrates reveals VPS15-dependent ULK/VPS34 interplay in the regulation of autophagy.

EMBO J 2021 06 14:e105985. Epub 2021 Jun 14.

Molecular Cell Biology of Autophagy, The Francis Crick Institute, London, UK.

Autophagy is a process through which intracellular cargoes are catabolised inside lysosomes. It involves the formation of autophagosomes initiated by the serine/threonine kinase ULK and class III PI3 kinase VPS34 complexes. Here, unbiased phosphoproteomics screens in mouse embryonic fibroblasts deleted for Ulk1/2 reveal that ULK loss significantly alters the phosphoproteome, with novel high confidence substrates identified including VPS34 complex member VPS15 and AMPK complex subunit PRKAG2. Read More

View Article and Full-Text PDF

Talin mechanosensitivity is modulated by a direct interaction with cyclin-dependent kinase-1.

J Biol Chem 2021 Jun 9:100837. Epub 2021 Jun 9.

School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK. Electronic address:

Talin (TLN1) is a mechanosensitive component of adhesion complexes that directly couples integrins to the actin cytoskeleton. In response to force, talin undergoes switch-like behavior of its multiple rod domains that modulate interactions with its binding partners. Cyclin-dependent kinase-1 (CDK1) is a key regulator of the cell cycle, exerting its effects through synchronized phosphorylation of a large number of protein targets. Read More

View Article and Full-Text PDF

The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals an Arpp19/PP2A-B55 feedback loop.

Nat Commun 2021 06 11;12(1):3565. Epub 2021 Jun 11.

Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237, Montpellier, France.

Arpp19 is a potent PP2A-B55 inhibitor that regulates this phosphatase to ensure the stable phosphorylation of mitotic/meiotic substrates. At G2-M, Arpp19 is phosphorylated by the Greatwall kinase on S67. This phosphorylated Arpp19 form displays a high affinity to PP2A-B55 and a slow dephosphorylation rate, acting as a competitor of PP2A-B55 substrates. Read More

View Article and Full-Text PDF

Gene-environment interactions mediate stress susceptibility and resilience through the CaMKIIβ/TARPγ-8/AMPAR pathway.

iScience 2021 May 2;24(5):102504. Epub 2021 May 2.

SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

Although stressful events predispose individuals to psychiatric disorders, such as depression, not all people who undergo a stressful life experience become depressed, suggesting that gene-environment interactions (GxE) determine depression risk. The ventral hippocampus (vHPC) plays key roles in motivation, sociability, anhedonia, despair-like behaviors, anxiety, sleep, and feeding, pointing to the involvement of this brain region in depression. However, the molecular mechanisms underlying the cross talk between the vHPC and GxE in shaping behavioral susceptibility and resilience to chronic stress remain elusive. Read More

View Article and Full-Text PDF

Measuring pathway database coverage of the phosphoproteome.

PeerJ 2021 25;9:e11298. Epub 2021 May 25.

Division of Bioinformatics, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

Protein phosphorylation is one of the best known post-translational mechanisms playing a key role in the regulation of cellular processes. Over 100,000 distinct phosphorylation sites have been discovered through constant improvement of mass spectrometry based phosphoproteomics in the last decade. However, data saturation is occurring and the bottleneck of assigning biologically relevant functionality to phosphosites needs to be addressed. Read More

View Article and Full-Text PDF

cAMP-Dependent Signaling Pathways as Potential Targets for Inhibition of Blood Stages.

Front Microbiol 2021 24;12:684005. Epub 2021 May 24.

Unité de Biologie de Plasmodium et Vaccins, Département de Parasites et Insectes Vecteurs, Institut Pasteur, Paris, France.

We review the role of signaling pathways in regulation of the key processes of merozoite egress and red blood cell invasion by and, in particular, the importance of the second messengers, cAMP and Ca, and cyclic nucleotide dependent kinases. cAMP-dependent protein kinase (PKA) is comprised of cAMP-binding regulatory, and catalytic subunits. The less well conserved cAMP-binding pockets should make cAMP analogs attractive drug leads, but this approach is compromised by the poor membrane permeability of cyclic nucleotides. Read More

View Article and Full-Text PDF

Development of immunoprecipitation - two-dimensional liquid chromatography - mass spectrometry methodology as biomarker read-out to quantify phosphorylated tau in cerebrospinal fluid from Alzheimer disease patients.

J Chromatogr A 2021 May 28;1651:462299. Epub 2021 May 28.

R&D Neurosciences, Janssen Pharmaceutica, Turnhoutseweg 30, Beerse, Belgium. Electronic address:

In Alzheimer's disease (AD) brain, one of the histopathological hallmarks is the neurofibrillary tangles consisting of aggregated and hyperphosphorylated tau. Currently many tau binding antibodies are under development to target the extracellular species responsible for the spreading of the disease in the brain. As such, an in-house developed antibody JNJ-63733657 with picomolar affinity towards tau phosphorylated at both T212 and T217 (further named p217+tau) was recently tested in phase I clinical trial NCT03375697. Read More

View Article and Full-Text PDF

Wnt5a modulates dendritic spine dynamics through the regulation of Cofilin via small Rho GTPase activity in hippocampal neurons.

J Neurochem 2021 Jun 9. Epub 2021 Jun 9.

Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

Dendritic spines are small, actin-rich protrusions that act as the receiving sites of most excitatory inputs in the central nervous system. The remodeling of the synapse architecture is mediated by actin cytoskeleton dynamics, a process precisely regulated by the small Rho GTPase family. Wnt ligands exert their pre- and postsynaptic effects during formation and consolidation of the synaptic structure. Read More

View Article and Full-Text PDF

Phosphorylation of Trans-active response DNA binding protein-of 43 kDa promotes its cytoplasmic aggregation and modulates its function in tau mRNA stability and exon 10 alternative splicing.

J Neurochem 2021 Jun 9. Epub 2021 Jun 9.

Key Laboratory of Neuroregeneration and Ministry of Education of Jiangsu, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research, Evaluation of Tissue Engineering Technology Products.

Trans-active response DNA-binding protein of 43 kDa (TDP-43) promotes tau mRNA instability and tau exon 10 inclusion. Aggregation of phosphorylated TDP-43 is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). CK1ε phosphorylates TDP-43 at multiple sites, enhances its cytoplasmic aggregation and modu-lates its function in tau mRNA processing. Read More

View Article and Full-Text PDF

Convergent NMDA receptor-Pannexin1 signaling pathways regulate the interaction of CaMKII with Connexin-36.

Commun Biol 2021 Jun 8;4(1):702. Epub 2021 Jun 8.

Department of Biology, York University, Toronto, ON, Canada.

Ca/calmodulin-dependent protein kinase II (CaMKII) binding and phosphorylation of mammalian connexin-36 (Cx36) potentiate electrical coupling. To explain the molecular mechanism of how Cx36 modifies plasticity at gap junctions, we investigated the roles of ionotropic N-methyl-D-aspartate receptors and pannexin1 (Panx1) channels in regulating Cx36 binding to CaMKII. Pharmacological interference and site-directed mutagenesis of protein interaction sites shows that NMDA receptor activation opens Cx36 channels, causing the Cx36- CaMKII binding complex to adopt a compact conformation. Read More

View Article and Full-Text PDF

Sugar phosphate activation of the stress sensor eIF2B.

Nat Commun 2021 06 8;12(1):3440. Epub 2021 Jun 8.

Calico Life Sciences LLC, South San Francisco, CA, USA.

The multi-subunit translation initiation factor eIF2B is a control node for protein synthesis. eIF2B activity is canonically modulated through stress-responsive phosphorylation of its substrate eIF2. The eIF2B regulatory subcomplex is evolutionarily related to sugar-metabolizing enzymes, but the biological relevance of this relationship was unknown. Read More

View Article and Full-Text PDF

Evolutionary crossroads of cell signaling: PP1 and PP2A substrate sites in intrinsically disordered regions.

Biochem Soc Trans 2021 Jun 8. Epub 2021 Jun 8.

Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Schänzlestraße 18, 79104 Freiburg, Germany.

Phosphorylation of the hydroxyl group of the amino acids serine and threonine is among the most prevalent post-translational modifications in mammalian cells. Phospho-serine (pSer) and -threonine (pThr) represent a central cornerstone in the cell's toolbox for adaptation to signal input. The true power for the fast modulation of the regulatory pSer/pThr sites arises from the timely attachment, binding and removal of the phosphate. Read More

View Article and Full-Text PDF

Comprehensive Phosphoproteomic Analysis of in Response to Dehydration Provides Insights into Plant ROS Signaling Transduction.

ACS Omega 2021 Jun 17;6(21):13554-13566. Epub 2021 May 17.

School of Life Sciences, Ningxia University, Yinchuan 750021, China.

Terrestrial cyanobacteria, originated from aquatic cyanobacteria, exhibit a unique mechanism for drought adaptation during long-term evolution. To elucidate this diverse adaptive mechanism exhibited by terrestrial cyanobacteria from the post-translation modification aspect, we performed a global phosphoproteome analysis on the abundance of phosphoproteins in response to dehydration using , a kind of terrestrial cyanobacteria having strong ecological adaptability to xeric environments. A total of 329 phosphopeptides from 271 phosphoproteins with 1168 phosphorylation sites were identified. Read More

View Article and Full-Text PDF

Phosphorylation in Novel Mitochondrial Creatine Kinase Tyrosine Residues Render Cardioprotection against Hypoxia/Reoxygenation Injury.

J Lipid Atheroscler 2021 May 19;10(2):223-239. Epub 2021 Jan 19.

Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutics Center, Inje University, Busan, Korea.

Objective: Ischemic cardiomyopathy (ICM) is the leading cause of heart failure. Proteomic and genomic studies have demonstrated ischemic preconditioning (IPC) can assert cardioprotection against ICM through mitochondrial function regulation. Considering IPC is conducted in a relatively brief period, regulation of protein expression also occurs very rapidly, highlighting the importance of protein function modulation by post-translational modifications. Read More

View Article and Full-Text PDF

Reduction of mechanical loading in tendons induces heterotopic ossification and activation of the β-catenin signaling pathway.

J Orthop Translat 2021 Jul 18;29:42-50. Epub 2021 May 18.

Division of Orthopaedic Surgery, Department of Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

Background: Tendons are the force transferring tissue that enable joint movement. Excessive mechanical loading is commonly considered as a primary factor causing tendinopathy, however, an increasing body of evidence supports the hypothesis that overloading creates microdamage of collagen fibers resulting in a localized decreased loading on the cell population within the damaged site. Heterotopic ossification is a complication of late stage tendinopathy, which can significantly affect the mechanical properties and homeostasis of the tendon. Read More

View Article and Full-Text PDF

The poly(ADP-ribosyl)ation of BRD4 mediated by PARP1 promoted pathological cardiac hypertrophy.

Acta Pharm Sin B 2021 May 14;11(5):1286-1299. Epub 2020 Dec 14.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou 510006, China.

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. Read More

View Article and Full-Text PDF

Rats Display Sexual Dimorphism in Phosphorylation of Brain Tau with Age.

J Alzheimers Dis 2021 Jun 3. Epub 2021 Jun 3.

Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.

Background: Women have a two-fold higher risk than men to Alzheimer's disease (AD) at midlife. Larger brain tau burden was consistently shown in older women than age-matched men. The biological basis for this gender disparity remains elusive. Read More

View Article and Full-Text PDF

"Don't Phos Over Tau": recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer's disease and other tauopathies.

Mol Neurodegener 2021 Jun 5;16(1):37. Epub 2021 Jun 5.

Department of Neuroscience, College of Medicine, University of Florida, BMS J483/CTRND, 1275 Center Drive, Gainesville, FL, 32610, USA.

Phosphorylation is one of the most prevalent post-translational modifications found in aggregated tau isolated from Alzheimer's disease (AD) patient brains. In tauopathies like AD, increased phosphorylation or hyperphosphorylation can contribute to microtubule dysfunction and is associated with tau aggregation. In this review, we provide an overview of the structure and functions of tau protein as well as the physiologic roles of tau phosphorylation. Read More

View Article and Full-Text PDF

Phosphorylation of human phospholipase A1 DDHD1 at newly identified phosphosites affects its subcellular localization.

J Biol Chem 2021 Jun 2:100851. Epub 2021 Jun 2.

Faculty of Pharma-Science, Teikyo University, 2-11-1 Kaga, Itabashi-Ku, Tokyo 173-8605, Japan. Electronic address:

Phospholipase A1 (PLA1) hydrolyzes the fatty acids of glycerophospholipids, which are structural components of the cellular membrane. Genetic mutations in DDHD1, an intracellular PLA1, result in hereditary spastic paraplegia (HSP) in humans. However, the regulation of DDHD1 activity has not yet been elucidated in detail. Read More

View Article and Full-Text PDF

NR4A1 enhances MKP7 expression to diminish JNK activation induced by ROS or ER-stress in pancreatic β cells for surviving.

Cell Death Discov 2021 Jun 4;7(1):133. Epub 2021 Jun 4.

Department of Cell Biology, Shandong University School of Medicine, Jinan, China.

Under adverse conditions, such as sustained or chronic hyperglycemia or hyperlipidemia, ROS (reactive oxygen species) or/and ER-stress (endoplasmic reticulum stress) will be induced in pancreatic β cells. ROS or ER-stress damages β-cells even leads to apoptosis. Previously we found ROS or ER-stress resulted in JNK activation in β cells and overexpressing NR4A1 in MIN6 cells reduced JNK activation via modulating cbl-b expression and subsequent degrading the upstream JNK kinase (MKK4). Read More

View Article and Full-Text PDF

CSF-1/CSF-1R Signaling Inhibitor Pexidartinib (PLX3397) Reprograms Tumor-Associated Macrophages and Stimulates T-Cell Infiltration in the Sarcoma Microenvironment.

Mol Cancer Ther 2021 Jun 4. Epub 2021 Jun 4.

Orthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center

Colony-stimulating factor 1 (CSF-1) is a primary regulator of the survival, proliferation, and differentiation of monocyte/macrophage that sustains the pro-tumorigenic functions of tumor-associated macrophages (TAMs). Considering current advances in understanding the role of the inflammatory tumor microenvironment, targeting the components of the sarcoma microenvironment, such as TAMs, is a viable strategy. Here, we investigated the effect of PLX3397 (pexidartinib) as a potent inhibitor of the CSF-1 receptor (CSF-1R). Read More

View Article and Full-Text PDF

Use of Mitotic Protein Kinase Inhibitors and Phospho-Specific Antibodies to Monitor Protein Phosphorylation During the Cell Cycle.

Methods Mol Biol 2021 ;2329:205-221

Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.

Reversible protein phosphorylation regulates the transitions between different phases of the cell cycle ensuring proper segregation of the duplicated genome into two daughter cells. Protein kinases and protein phosphatases establish the appropriate phosphorylation stoichiometries in diverse substrates maintaining genomic stability as a cell undergoes this complex process. Along with regulating common substrates, these opposing enzymes regulate one another by fine-tuning each other's activity both spatially and temporally throughout mitosis. Read More

View Article and Full-Text PDF
January 2021

Polyglutamylase activity of tubulin tyrosine ligase-like 4 is negatively regulated by the never in mitosis gene A family kinase never in mitosis gene A -related kinase 5.

World J Biol Chem 2021 May;12(3):38-51

Faculty of Pharmaceutical Sciences, University of Campinas, Campinas 13083-862, Brazil.

Background: Tubulins, building blocks of microtubules, are modified substrates of diverse post-translational modifications including phosphorylation, polyglycylation and polyglutamylation. Polyglutamylation of microtubules, catalyzed by enzymes from the tubulin tyrosine ligase-like (TTLL) family, can regulate interactions with molecular motors and other proteins. Due to the diversity and functional importance of microtubule modifications, strict control of the TTLL enzymes has been suggested. Read More

View Article and Full-Text PDF

Phosphorylation-Dependent control of arc protein by TNIK.

J Neurochem 2021 Jun 2. Epub 2021 Jun 2.

Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road E, Guelph, ON, N1G 2W1, Canada.

Activity-regulated cytoskeleton-associated protein (Arc) is an immediate-early gene product that support neuroplastic changes important for cognitive function and memory formation. As a protein with homology to the retroviral Gag protein, a particular characteristic of Arc is its capacity to self-assemble into virus-like capsids that can package mRNAs and transfer those transcripts to other cells. Although a lot has been uncovered about the contributions of Arc to neuron biology and behavior, very little is known about how different functions of Arc are coordinately regulated both temporally and spatially in neurons. Read More

View Article and Full-Text PDF

AMPK in the gut-liver-brain axis and its influence on OP rats in an HSHF intake and WTD rat model.

Pflugers Arch 2021 Jun 1. Epub 2021 Jun 1.

Biosciences Department, Institute of Health and Society, Federal University of São Paulo, Campus Baixada Santista - UNIFESP/BS, Santos, São Paulo, 11015-020, Brazil.

Obesogenic diets (ODs) can affect AMPK activation in several sites as the colon, liver, and hypothalamus. OD intake can impair the hypothalamic AMPK regulation of energy homeostasis. Despite consuming ODs, not all subjects have the propensity to develop or progress to obesity. Read More

View Article and Full-Text PDF

Charting protein dephosphorylation triggered by Toll-like receptor (TLR) signaling in macrophages and its role in health and disease.

Int Rev Cell Mol Biol 2021 2;361:211-243. Epub 2021 Mar 2.

Department of Microbiology & Immunology, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New York, NY, United States.

Toll-like receptor (TLR) signaling induces substantial changes in the phosphoproteome of innate immune cells, mainly in the form of increased phosphorylation of signaling intermediaries. Loss of constitutive phosphorylation occurs simultaneously, but these transitions from a stable, phosphorylated state in resting cells to a sustained underphosphorylated state in activated cells have received far less attention. This review provides an overview of phosphorylation sites downregulated during TLR-mediated signaling, with a particular focus on TLR4 activation by lipopolysaccharide (LPS). Read More

View Article and Full-Text PDF

δ-Catenin Participates in EGF/AKT/p21 Signaling and Induces Prostate Cancer Cell Proliferation and Invasion.

Int J Mol Sci 2021 May 18;22(10). Epub 2021 May 18.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju 61186, Korea.

Prostate cancer (PCa) is the second most leading cause of death in males. Our previous studies have demonstrated that δ-catenin plays an important role in prostate cancer progression. However, the molecular mechanism underlying the regulation of δ-catenin has not been fully explored yet. Read More

View Article and Full-Text PDF