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CaMKIIProtein phosphorylationRegulatesCREBMyosin light chainsProteinsMultifunctionalSerine residuesDependentHippocampusResiduesDetermined by western blotStimulatesBiochemicalParticipatesRegulationNeuronsSynapticSubunitMitogen-activaAffinityBindsDephosphorylationIsoformPhosphopeptidesIncreasesDownstreamInhibitsMoleculeMetabolismModulationAntibodyImplicationsVitroActivationRegulatoryMGluR1OccursSubstrateCalcium-bindingSitesHumanDomainShowResultsStateChannelsFoundSmooth muscleEffect

CaMKII21

• We found that Homer3, the predominant isoform in Purkinje cells, is phosphorylated by calcium/calmodulin-dependent protein kinase II (CaMKII) both in vitro and in vivo . (jneurosci.org)
• In P/Q-type voltage-gated-Ca 2+ channel knock-out mice, in which CaMKII activation was reduced, the levels of Homer3 phosphorylation and the soluble form of Homer 3 were markedly lower. (jneurosci.org)
• Furthermore, both robust phosphorylation of Homer3 and its dissociation from metabotropic glutamate receptor 1α (mGluR1α) were triggered by depolarization in primary cultured Purkinje cells, and these events were inhibited by CaMKII inhibitor. (jneurosci.org)
• Together, these findings suggested that Homer3 in Purkinje cells might function as a reversible coupler regulated by CaMKII phosphorylation and that the phosphorylation is capable of regulating the postsynaptic molecular architecture in response to synaptic activity. (jneurosci.org)
• In this study, we revealed that Homer3 was phosphorylated by calcium/calmodulin-dependent protein kinase II (CaMKII) in Purkinje cells, and the phosphorylation reduces the affinity for Homer target molecules, resulting in change of the solubility. (jneurosci.org)
• Calmodulin variant E140G associated with long QT syndrome impairs CaMKIIδ autophosphorylation and L-type calcium channel inactivation. (nih.gov)
• Here we show that calcium/calmodulin-dependent kinase II (CaMKII) signals specifically to HDAC4 by binding to a unique docking site that is absent in other class IIa HDACs. (jci.org)
• Phosphorylation of HDAC4 by CaMKII promotes nuclear export and prevents nuclear import of HDAC4, with consequent derepression of HDAC target genes. (jci.org)
• In cardiomyocytes, CaMKII phosphorylation of HDAC4 results in hypertrophic growth, which can be blocked by a signal-resistant HDAC4 mutant. (jci.org)
• All subtypes are closely associated with calmodulin and FK506-binding protein and are modulated through phosphorylation by PKA, PKC, PKG and CaMKII. (novusbio.com)
• B ) Cartoon representation of activation of CaMKII by calcium:calmodulin (top) and proposed mechanism for spread of kinase activity (bottom). (elifesciences.org)
• Western blot detection of CaMKII KD phosphorylation by CaMKII WT . (elifesciences.org)
• C ) Western blot showing there is no phosphorylation signal from pT286 antibody on CaMKII KD (4 μM) when CaMKII WT is omitted from the kinase reaction. (elifesciences.org)
• D ) Western blot showing that 10 nM CaMKII WT (as included on the gels in panels A and B) gives no phosphorylation signal from the pT286 antibody. (elifesciences.org)
• Radioactivity detection of CaMKII KD phosphorylation by CaMKII WT . (elifesciences.org)
• These included the protein extracellular signal-regulated kinase (ERK), calcium/calmodulin-dependent kinase IIα (CaMKIIα), CaMKIIβ, CaMKIV, and the cAMP-response element binding protein (CREB). (sophia.ac.jp)
• The researchers then studied the effects of ramelteon and AMK on the phosphorylation of ERK, CaMKIIα, CaMKIIβ, CaMKIV, and CREB in the male mouse brain after sacrificing the rodents using standard protocols. (sophia.ac.jp)
• However, these drugs significantly decreased CaMKIIα/β phosphorylation in the same brain region. (sophia.ac.jp)
• In the perirhinal cortex (PRC), which is also associated with memory functions, both ramelteon and AMK significantly increased ERK, and only ramelteon significantly increased CaMKIIβ phosphorylation. (sophia.ac.jp)
• We show that phosphorylation of synGAP by Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII) decreases its affinity for the PDZ domains as much as 10-fold, measured by surface plasmon resonance. (caltech.edu)
• Therefore, we hypothesize that phosphorylation by CaMKII reduces synGAP′s ability to restrict binding of other proteins to the PDZ domains of PSD-95. (caltech.edu)

Protein phosphorylation4

• Suggestion of a role for protein phosphorylation in the regulation of intestinal active NaCl transport was found by studying the effects of low concentrations of promethazine on Ca 2+ -calmodulin (CaM)-dependent protein phosphorylation of ileal microvillus membranes and on active ileal electrolyte transport. (johnshopkins.edu)
• Both calcium/calmodulin and protein phosphorylation mechanisms control its activity. (antikoerper-online.de)
• We hypothesized that an imbalance of Ca2+/calmodulin dependent protein phosphorylation-dephosphorylation may be involved in delayed neuronal death after ischemia. (nih.gov)
• Wegmann S , Biernat J, Mandelkow E . A current view on Tau protein phosphorylation in Alzheimer's disease. (neurotree.org)

Regulates4

• Calcium-induced activation of calmodulin regulates and modulates the function of cardiac ion channels. (nih.gov)
• NCS1 regulates G protein-coupled receptor phosphorylation in a calcium-dependent manner and can substitute for calmodulin. (prospecbio.com)
• NCS1 regulates GRK1 and substitutes for calmodulin. (prospecbio.com)
• The phosphorylation of MLC primarily regulates the force production and maintenance in the smooth muscle [ 6 ]. (hindawi.com)

CREB3

• These results suggest that NO contributes to L-LTP by stimulating guanylyl cyclase and cGMP-dependent protein kinase, which acts in parallel with PKA to increase phosphorylation of the transcription factor CREB. (jneurosci.org)
• Activity-dependent CREB phosphorylation: Convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway. (the-scientist.com)
• In the hippocampus, which is the learning and memory center of the mammalian brain, treatment with ramelteon/AMK significantly increased the phosphorylation of both ERK and CREB. (sophia.ac.jp)

Myosin light chains1

• With less calcium available to combine with calmodulin, there is less activation of myosin light chain kinase and phosphorylation of myosin light chains ( click here for details ). (cvpharmacology.com)

Proteins10

• This gene encodes one of three calmodulin proteins which are members of the EF-hand calcium-binding protein family. (nih.gov)
• As it binds calcium, calmodulin undergoes conformational changes which can increase its affinity for target proteins. (thermofisher.com)
• Carbon disulfide inhalation increases Ca2+/calmodulin-dependent kinase phosphorylation of cytoskeletal proteins in the rat central nervous system. (cdc.gov)
• The alpha isoform is responsible for synaptic plasticity and participates in memory through its phosphorylation of synaptic proteins. (elifesciences.org)
• While short- and long-term memory formation has been associated with the phosphorylation levels of key memory-related proteins, the molecular mechanisms underlying melatonin-induced memory enhancement have remained elusive. (sophia.ac.jp)
• It is also known that the formation of both short- and long-term memories require the phosphorylation of certain memory-related proteins. (sophia.ac.jp)
• In addition, they examined "phosphorylation," or the biochemical addition of phosphate groups to protein structures, in five key proteins involved in memory formation. (sophia.ac.jp)
• PKC phosphorylation of these proteins also inhibits their binding to RNA in vitro. (embl.de)
• Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. (embl.de)
• A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. (bvsalud.org)

Multifunctional2

• Multifunctional calcium and calmodulin-dependent kinase II in neuronal function and disease. (vcu.edu)
• A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. (curehunter.com)

Serine residues2

• Multiple serine/threonine kinases control the subcellular localization of these HDACs by phosphorylation of common serine residues, but whether certain class IIa HDACs respond selectively to specific kinases has not been determined. (jci.org)
• Phosphorylation of serine residues in the N-terminus modulates the activity of ACA8, a plasma membrane Ca2+-ATPase of Arabidopsis thaliana / S. Giacometti, C.A. Marrano, M.C. Bonza, L. Luoni, M. Limonta, M.I. De Michelis. (unimi.it)

Dependent12

• An in vitro binding kinetic analysis revealed that these phosphorylation-dependent events were attributable to a decrease in the affinity of phosphorylated Homer3 for its ligand. (jneurosci.org)
• The similar, and unusual sensitivity to low concentrations of promethazine on ileal microvillus membrane phosphorylation increased by Ca 2+ -CaM and on ileal electrolyte transport is consistent with Ca 2+ -CaM-dependent microvillus membrane phosphorylation being involved in the regulation of active electrolyte transport in ileal absorptive cells. (johnshopkins.edu)
• It is also a substrate for the cyclic AMP-dependent protein kinase, calcium/calmodulin- dependent protein kinase II, and protein kinase C in vitro. (antikoerper-online.de)
• eEF2 is itself regulated by inhibitory phosphorylation at Thr56 by an upstream kinase, eEF2 kinase (eEF2K), also known as calmodulin-dependent protein kinase III. (nature.com)
• Immunohistochemical and biochemical investigations of Ca2+/calmodulin-dependent protein kinase II(CaM kinase II) and protein phosphatase (calcineurin) after transient forebrain ischemia demonstrated that the activity of CaM kinase II was decreased in the CA1 region of the hippocampus early (6-12 hours) after ischemia. (nih.gov)
• Calcium/calmodulin-dependent kinase II phosphorylation of the GABAA receptor alpha 1 subunit modulates benzodiazepine binding. (vcu.edu)
• It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. (curehunter.com)
• The Pyk2 mediated activation of ERK1/2 phosphorylation is also Src-, calmodulin- and protein kinase C-dependent. (uwo.ca)
• It is suggested that the phosphorylation of MLC catalyzed by Ca 2+ -calmodulin- (CAM-) dependent MLCK and dephosphorylation catalyzed by MLCP help regulate the contraction and relaxation of smooth muscle [ 8 , 9 ]. (hindawi.com)
• Synthetic peptide corresponding to aa 281-294 (M 281 HRQET(PSO 3 )VDCLKKFN 294 ) of the α-subunit of mouse and rat CaM kinase II (Ca 2+ /Calmodulin-dependent Protein Kinase II) thiophosphorylated at (Thr 286 ). (enzolifesciences.com)
• The effect of phosphorylation by cyclic GMP-dependent protein kinase (G-kinase) on the activity of the plasmalemmal Ca2+-transport ATPase was studied on isolated plasma membranes and on the ATPase purified from pig erythrocytes and from the smooth muscle of pig stomach and pig aorta. (portlandpress.com)
• In healthy individuals, nicotine improves memory impairment caused by sleep deprivation by enhancing the phosphorylation of calmodulin‑dependent protein kinase II, an essential regulator of cell proliferation and synaptic plasticity. (spandidos-publications.com)

Hippocampus1

• In the hippocampus/PRC, ramelteon/AMK did not affect the phosphorylation of CaMKIV. (sophia.ac.jp)

Residues1

• Short calmodulin-binding motif containing conserved Ile and Gln residues. (embl.de)

Determined by western blot2

• Changes in eEF2 phosphorylation were determined by western blot analyses. (nature.com)
• Half-time of maximum phosphorylation (t 1⁄2 =1.1 ± 0.2 min) determined by western blot, using an antibody against pT286. (elifesciences.org)

Stimulates2

• The activation of endogenous mGluR1 in primary mouse cortical neuron stimulates ERK1/2 phosphorylation. (uwo.ca)
• It is proposed that G-kinase stimulates the plasmalemmal Ca2+ pump of smooth-muscle cells indirectly via the phosphorylation of an associated PI kinase. (portlandpress.com)

Biochemical1

• Rather, mass photometry, crosslinking mass spectrometry, single molecule TIRF microscopy and biochemical assays identify inter-holoenzyme phosphorylation (IHP) as the mechanism for spreading phosphorylation. (elifesciences.org)

Participates1

• Studies have found that calmodulin participates in the regulation of several biological processes including energy and biosynthetic metabolism, cell motility, exocytosis, cytoskeletal assembly, and intracellular modulation of both cAMP and calcium concentrations. (thermofisher.com)

Regulation3

• Cohen, ME, Sharp, GWG & Donowitz, M 1986, ' Suggestion of a role for calmodulin and phosphorylation in regulation of rabbit ileal electrolyte transport: Effects of promethazine ', American Journal of Physiology - Gastrointestinal and Liver Physiology , vol. 251, no. 5, pp. 14/5. (johnshopkins.edu)
• The phosphorylation state of eEF2 is directly linked to synaptic plasticity regulation [ 23 ] and learning, and in the context of cue-induced drug seeking, dephosphorylation of both eEF2 and eIF2α occurs. (nature.com)
• The major projects ongoing in the laboratory focus on three major areas: 1) Modulation of GABAA receptor function, 2) Modulation of Ca2+-regulated phosphorylation and dephosphorylation systems and 3) Regulation of free intracellular Ca2+ homeostasis. (vcu.edu)

Neurons1

• Treatments that prevent Pyk2 phosphorylation in cortical neurons, and the overexpression of Pyk2 dominant-negative and catalytically inactive Pyk2 mutants in HEK293 cells, prevent ERK1/2 phosphorylation. (uwo.ca)

Synaptic1

• These results suggest that the phosphorylation may regulate postsynaptic molecular architecture and Ca 2+ signaling of Purkinje cells in response to synaptic activity. (jneurosci.org)

Subunit1

• This antibody does not detect the non-phosphorylated α-subunit of rat CaM kinase II nor the ~60kDa β-subunit in either phosphorylation state. (enzolifesciences.com)

Mitogen-activa1

• We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kDa ribosomal S6 kinase (RSK) and mitogen-activated protein kinase (MAP kinase), contribute to the serum-induced phosphorylation of c-Fos. (nih.gov)

Affinity1

• G-kinase, but not A-kinase, stimulated the phosphorylation of PI to phosphatidylinositol phosphate (PIP) in a preparation of (Ca2+ + Mg2+)-ATPase obtained by calmodulin affinity chromatography from smooth muscle, but not in a similar preparation from erythrocytes. (portlandpress.com)

Binds1

• The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain. (embl.de)

Dephosphorylation1

• EA caused a significant increase in the MLC dephosphorylation and MLCK phosphorylation levels in the group compared to the sham EA and model groups. (hindawi.com)

Isoform1

• ACA8 is a plasma membrane-localized isoform of calmodulin (CaM)-regulated Ca2+-ATPase of Arabidopsis thaliana. (unimi.it)

Phosphopeptides1

• The major phosphopeptides derived from biosynthetically labeled c-Fos correspond to phosphopeptides generated after phosphorylation of c-Fos in vitro with both RSK and MAP kinase. (nih.gov)

Increases2

• Promethazine inhibited the Ca 2+ -CaM-induced increases in each of these phosphorylations. (johnshopkins.edu)
• Fig. 6: Pirenzepine upregulates MeCP2 phosphorylation and increases release probability. (nature.com)

Downstream1

• This study suggests a role for nuclear RSK and MAP kinase in modulating newly synthesized c-Fos phosphorylation and downstream signaling. (nih.gov)

Inhibits2

• Protein kinase C-mediated phosphorylation of the Serine at 41 within this site inhibits this interaction. (neuromics.com)
• Interestingly, PKC phosphorylation of EWS inhibits its binding to RNA homopolymers, and conversely, RNA binding to EWS interferes with PKC phosphorylation. (embl.de)

Molecule1

• The molecule may utilize the IQ domain to bind calmodulin. (neuromics.com)

Metabolism1

• Gene therapy displacement of endogenous MCUb with a dominant-negative MCUb transgene (MCUb W246R/V251E ) in vivo rescued T2D cardiomyocytes from metabolic inflexibility and stimulated cardiac contractile function and adrenergic responsiveness by enhancing phospholamban phosphorylation via protein kinase A. We conclude that MCUb represents one newly discovered molecular effector at the interface of metabolism and cardiac function, and its repression improves the outcome of the chronically stressed diabetic heart. (diabetesjournals.org)

Modulation1

• The possible physiological implications of the subtle modulation of ACA8 activity by phosphorylation of its N-terminus are discussed. (unimi.it)

Antibody1

• The following product was used in this experiment: Phospho-Calmodulin 1/2/3 (Thr79, Ser81) Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-104932, RRID AB_2816405. (thermofisher.com)

Implications1

• Subtype Differences in the Interaction of HIV-1 Matrix with Calmodulin: Implications for Biological Functions. (nih.gov)

Vitro1

• Cooperative phosphorylation at these sites by both enzymes was observed in vitro and reflected in vivo by the predominance of the peptide phosphorylated on both sites, as opposed to singly phosphorylated peptides. (nih.gov)

Activation2

• In a heterologous system, the Ca 2+ signaling pattern induced by mGluR1α activation was modulated by the Homer3 phosphorylation state. (jneurosci.org)
• This results in the release of Ca2+ from intracellular stores and the activation of protein kinase C. The activation of Group I mGluRs also results in ERK1/2 phosphorylation. (uwo.ca)

Regulatory1

• The phosphorylation of smooth muscle regulatory light chain by MLCK is the basic requirement for smooth muscle contraction and hollow organ physiological activities [ 10 ]. (hindawi.com)

MGluR11

• Moreover, the phosphorylation altered Ca 2+ signaling patterns induced by mGluR1α in heterologous expression system. (jneurosci.org)

Occurs1

• Evidence is presented showing that the apparent phosphorylation occurs in a contaminant protein, possibly myosin light-chain kinase. (portlandpress.com)

Substrate1

• Time-resolved DEER EPR and solid-state NMR afford kinetic and structural elucidation of substrate binding to Ca(2+)-ligated calmodulin. (nih.gov)

Calcium-binding1

• Calmodulin is a small, highly conserved calcium binding protein found in all eukaryotic cells. (thermofisher.com)

Sites4

• The growth-regulated enzymes responsible for this phosphorylation in early G1 phase of the cell cycle and the sites of phosphorylation have not been identified. (nih.gov)
• The phosphorylation sites identified for RSK (Ser-362) and MAP kinase (Ser-374) are in the transrepression domain. (nih.gov)
• Yellow circles indicate phosphorylation sites. (elifesciences.org)
• Rat GAP-43 is a 226 amino acid (aa) protein that contains an N-terminal lipid binding motif, an 11 aa IQ domain (IQ:Ile-Gln-X-Ser-etc) (aa 38 - 48), and a C-terminus with four potential serine phosphorylation sites. (neuromics.com)

Human3

• Calmodulin Mutations in Human Disease. (nih.gov)
• A synthesized peptide derived from human Calmodulin around the phosphorylation site of Thr79/Ser81. (thermofisher.com)
• Drepper F, Biernat J, Kaniyappan S, Meyer HE, Mandelkow EM , Warscheid B, Mandelkow E . A combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau but minimal levels of other key modifications. (neurotree.org)

Domain1

• Here we report that EWS, a nuclear RNA-binding prooncoprotein, contains an IQ domain, is phosphorylated by protein kinase C, and interacts with calmodulin. (embl.de)

Show1

• Here we show that methyl-CpG-binding protein 2 (MeCP2) phosphorylation at Ser421 (pMeCP2) is essential for the sustained, but not the rapid, antidepressant effects of ketamine and scopolamine in mice. (nature.com)

Results1

• In contrast with previous results of Furukawa & Nakamura [(1987) J. Biochem (Tokyo) 101, 287-290], no convincing evidence for a phosphorylation of the (Ca2+ + Mg2+)-ATPase was found. (portlandpress.com)

State1

• Here, we present evidence that Homer-mediated coupling is regulated by its phosphorylation state. (jneurosci.org)

Channels1

• Calmodulin Interactions with Voltage-Gated Sodium Channels. (nih.gov)

Found1

• To mimic phosphorylation of the ACA8 N-terminus, each of the serines found to be phosphorylated in those studies (Ser19, Ser22, Ser27, Ser29, Ser57, and Ser99) has been mutated to aspartate. (unimi.it)

Smooth muscle1

• The level of myosin light chain (MLC) phosphorylation is an important determinant of smooth muscle contraction. (hindawi.com)

Effect1

• The promethazine effect on microvillus membrane phosphorylation was specific, since neither cAMP- and cGMP-induced phosphorylation in the microvillus membrane nor the stimulation by Ca 2+ -CaM of myosin light chain kinase phosphorylation of myosin light chain were affected by promethazine. (johnshopkins.edu)