• Calcium mineral/calmodulin-dependent proteins kinase II (CaMKII) can be an autophosphorylating kinase (14,15) that constitutes up to 2% of total proteins in certain parts of the brain and it is extremely enriched at synapses (16). (healthyguide.info)
  • This CaMKII-phosphatase program satisfies the least requirements from the autophosphorylating kinase-phosphatase program described above, which is as a result possible Rabbit Polyclonal to Parkin a bistable CaMKII change forms the molecular basis of synaptic plasticity and long-term storage (21). (healthyguide.info)
  • Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is an important decoder of Ca(2+) signals and mediator of synaptic plasticity. (nih.gov)
  • We show that it involved an interaction with microtubular elements, required activation of the kinase, and led to localized dendritic CaMKII autophosphorylation. (nih.gov)
  • Furthermore, Ca 2+ -induced GTPase activity correlated with activation of protein kinase C and required a basal activity of Ca 2+ /calmodulin-dependent protein kinase II. (jneurosci.org)
  • Ca2+/Calmodulin dependent protein kinase (CaMK) are mammalian calmodulin-dependent calcium-dependent protein kinases activated by elevation of Ca+2 and calmodulin concentration to phosphorylate Ser and Thr. (proteopedia.org)
  • CaMKII is multifunctional kinase. (proteopedia.org)
  • Rellos P, Pike AC, Niesen FH, Salah E, Lee WH, von Delft F, Knapp S. Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation. (proteopedia.org)
  • CamKII-tTA transgenic mice are viable and fertile, with expression of the tetracycline-controlled transactivator protein (tTA) directed to forebrain neurons by the forebrain-specific calcium-calmodulin-dependent kinase II (Camk2a) promoter. (mmrrc.org)
  • Stratton studies Ca2+/calmodulin dependent protein kinase II (CaMKII), a calcium-sensitive protein encoded by four genes in mammals. (umass.edu)
  • CaMKII is an ubiquitously expressed serine/threonine protein kinase that is activated by Ca2+ and calmodulin (CaM) and has been implicated in regulation of the cell cycle and transcription. (thermofisher.com)
  • The dodecameric protein kinase CaMKII is expressed throughout the body. (elifesciences.org)
  • This manuscript reports the fundamental finding that an oligomeric protein kinase, CaMKII, can be phosphorylated by another molecule of the holoenzyme in a manner that does not involve subunit exchange. (elifesciences.org)
  • B ) Cartoon representation of activation of CaMKII by calcium:calmodulin (top) and proposed mechanism for spread of kinase activity (bottom). (elifesciences.org)
  • C ) Schematic representation of experiment performed in panel ( D ). ( D ) Kinase activity of CaMKII WT (10 nM) against CaMKII KD (4 μM). (elifesciences.org)
  • The CaMKII (calcium/calmodulin-dependent protein kinase II) pathway regulates key cellular processes and functions throughout the body, including retinal ganglion cells in the eye. (newswise.com)
  • Central to these events is a molecule called Calcium-Calmodulin dependent Kinase II (CaMKII). (nlmfoundation.org)
  • Ongoing work has focused on the structure and function of one ubiquitous Ca 2+ signal mediator, namely multifunctional Ca 2+ /calmodulin-dependent protein kinase II (CaMKII). (amc.edu)
  • 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)
  • E ) Kinase activity of EGFP-CaMKII WT and CaMKII KD -AviTag in HEK cells and HEK cell lysates. (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)
  • Li B, Shi Y, Shu J, Gao J, Wu P and Tang S-J, 2013 Wingless-type mammary tumor virus integration site family, member 5A (Wnt5a) regulates human immunodeficiency virus type1 (HIV-1) envelope glycoprotein 120 (gp 120)-induced expression of pro-inflammatory cytokines via the Ca2+/calmodulin-dependent protein kinase II (caMKII) and c-JUN N-terminal kinase (JNK) signaling pathways. (utmb.edu)
  • For this purpose, WIN 55,212-2 was injected in pregnant wistar rats from gestation day 5 to 20 and a detailed analysis of the levels of the neurotrophin brain-derived neurotrophic factor (BDNF) as well as of the signaling molecules extracellular signal-regulated kinase (ERK)1/2 and alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) was carried out in adult offspring. (researchgate.net)
  • We aim to study the coupling between LTCC and β adrenergic receptors in different cardiomyocyte microdomains, the distinct involvement of PKA and CAMKII (Ca2+/calmodulin-dependent protein kinase II) and explore how this functional complex is disrupted in heart failure.Methods:Global signaling between LTCCs and β adrenergic receptors was assessed with whole-cell current recordings and western blot analysis. (imperial.ac.uk)
  • 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)
  • Here we report that extinction is triggered by two hippocampal signaling pathways underlying retrieval (the cAMP-dependent protein kinase and the mitogen-activated protein kinase pathways) and two other mechanisms that become activated at the same time and are not necessary for retrieval (N-methyl-D-aspartate glutamatergic receptors and the calcium/calmodulin-dependent protein kinase II signaling pathway). (unboundmedicine.com)
  • The NR2B subunit of the NMDA receptor interacts with several prominent proteins in the postsynaptic density, including calcium/calmodulin-dependent protein kinase II (CaMKII). (caltech.edu)
  • This study investigated calcium/calmodulin kinase II (CaMKII) activity related to long-standing neuronal injury of the hippocampus in kainate (KA)-induced experimental temporal lobe epilepsy. (koreamed.org)
  • Through a series of experiments, Bers, his team, and their collaborators at Johns Hopkins University School of Medicine show that the moderate to high blood glucose levels characteristic of diabetes caused a sugar molecule (O-linked N-acetylglucosamine, or O-GlcNAc) in heart muscle cells to fuse to a specific site on a protein known as calcium/calmodulin-dependent protein kinase II, or CaMKII. (dentistrytoday.com)
  • Inhibition of the inositol trisphosphate receptor of mouse eggs and A7r5 cells by KN-93 via a mechanism unrelated to Ca2+/calmodulin-dependent protein kinase II antagonism. (umassmed.edu)
  • Inhibition of CaMKII abrogated the insulin-induced Erk-1/2 activation, DNA synthesis and phosphorylation of IRS-1 at S612. (cnr.it)
  • Inhibition of CaMKII also abrogated the down-regulation of insulin-stimulated Akt phosphorylation, Glut-4 membrane translocation and glucose uptake. (cnr.it)
  • Phosphorylation buy 1619903-54-6 of T286 is certainly significantly elevated after LTP induction (30C33), and CaMKII autonomy is necessary for LTP induction (34,35) and regular learning and storage (36). (healthyguide.info)
  • since DAT phosphorylation by CAMKII results in dopamine efflux in vivo, activation of transporter-coupled calcium channels is a potential mechanism by which certain drugs (e.g., amphetamine) trigger neurotransmitter release. (wikipedia.org)
  • A synthesized peptide derived from human CaMKII around the phosphorylation site of Ser235. (thermofisher.com)
  • 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)
  • Western blot detection of CaMKII KD phosphorylation by CaMKII WT . (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)
  • 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)
  • The disruption decreases Thr286 phosphorylation of alphaCaMKII, lowers phosphorylation of a key CaMKII substrate in the postsynaptic membrane (AMPA receptor subunit glutamate receptor 1), and produces deficits in hippocampal long-term potentiation and spatial learning. (caltech.edu)
  • In addition to its known accumulation at spines, we observed with live imaging the dynamic recruitment of CaMKII to dendritic subdomains adjacent to activated synapses in cultured hippocampal neurons. (nih.gov)
  • The ultimate goal is to figure out how long-term memory works at a molecular level by studying how CaMKII in neurons may act as a hub to maintain molecular signals over a long period of time. (umass.edu)
  • Here, we show that induction by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in neurons. (caltech.edu)
  • Calmodulin variant E140G associated with long QT syndrome impairs CaMKIIδ autophosphorylation and L-type calcium channel inactivation. (nih.gov)
  • Similarly, boosting CaMKII activity via gene therapy proved protective of retinal ganglion cells in glaucoma models based on elevated eye pressure or genetic deficiencies. (newswise.com)
  • Replacement of endogenous CaMKII with a mutant that cannot translocate within dendrites lessened this activity-dependent synaptic plasticity. (nih.gov)
  • Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning. (caltech.edu)
  • Together our results demonstrate the importance of interactions between CaMKII and NR2B for CaMKII activity, synaptic plasticity, and learning. (caltech.edu)
  • The prevailing hypothesis for the spread of CaMKII activity, involving shuffling of subunits between activated and naive holoenzymes, is broadly termed subunit exchange. (elifesciences.org)
  • The CaMKIIα-tTA transgene inserted on chromosome 12, resulting in a 508 kb deletion that affects five mouse genes: Vipr2 (vasoactive intestinal peptide receptor 2), Wdr60 (WD repeat-containing protein 60), Esyt2 (extended synaptotagmin-like protein 2), Ncapg2 (non-SMC condensin II complex, subunit G2), and Ptprn2 (protein tyrosine phosphatase, receptor type, N polypeptide 2). (alzforum.org)
  • Inhibition of CaMKII activity, for example, has been shown to be either protective or detrimental to retinal ganglion cells, depending on the conditions. (newswise.com)
  • Furthermore, a robust reduction of total and phospho-alpha-CaMKII was found in the hippocampus of rats prenatally exposed to WIN 55,212-2. (researchgate.net)
  • TY - JOUR T1 - The role of NMDA glutamate receptors, PKA, MAPK, and CAMKII in the hippocampus in extinction of conditioned fear. (unboundmedicine.com)
  • The following product was used in this experiment: Phospho-CaMKII alpha/beta/delta (Ser235) Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-105641, RRID AB_2817069. (thermofisher.com)
  • Using an antibody marker of CaMKII activity, Chen's team discovered that CaMKII pathway signaling was compromised whenever retinal ganglion cells were exposed to toxins or trauma from a crush injury to the optic nerve, suggesting a correlation between CaMKII activity and retinal ganglion cell survival. (newswise.com)
  • The Ca2+/calmodulin-dependent protein kinases (CaM kinases) comprise a structurally related subfamily of serine/threonine kinases which include CaMKI, CaMKII and CaMKIV. (thermofisher.com)
  • B ) An HDAC5 mutant, in which the CaMKII consensus sites were mutated to the corresponding sites in HDAC4, was expressed in COS cells alone or with CaMKI c.a. and CaMKIIδB-T287D. (jci.org)
  • This mutant was responsive to CaMKI but not to CaMKIIδB-T287D. (jci.org)
  • This gene encodes one of three calmodulin proteins which are members of the EF-hand calcium-binding protein family. (nih.gov)
  • Plakantonakis is interested in characterizing the interaction of CaMKII with other proteins that may be important in brain function. (nlmfoundation.org)
  • A ) Chimeric HDAC4/5 proteins (as indicated) were expressed in COS cells in the presence of CaMKIIδB-T287D. (jci.org)
  • D ) Cotransfection of FLAG-HDAC4 with either WT or constitutively activated Myc-CaMKIIδB-T287D. (jci.org)
  • We investigated the role of CaMKII in insulin signalling in a rat skeletal muscle cell line, demonstrating that CaMKII modulates the insulin action on DNA synthesis and the negative feedback that down regulates glucose uptake. (cnr.it)
  • Calcium-induced activation of calmodulin regulates and modulates the function of cardiac ion channels. (nih.gov)
  • One major aspect of our current effort is to use molecular/genetic approaches to manipulate CaMKII isozyme expression in order to test the concept that Ca 2+ signaling, via specific CaMKII isoforms, regulates VSM gene transcription and VSM phenotype-specific functions. (amc.edu)
  • 2 - after the initial stimulation of the IRS-1/Akt pathway, CaMKII mediates the down-regulation of stimulated glucose uptake. (cnr.it)
  • Our study is the first to show that activating the CaMKII pathway helps protect retinal ganglion cells from a variety of injuries and in multiple glaucoma models," said the study's lead investigator, Bo Chen, Ph.D., associate professor of ophthalmology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York City. (newswise.com)
  • Searching for ways to intervene, they found that activating the CaMKII pathway with gene therapy proved protective to the retinal ganglion cells. (newswise.com)
  • By using blockers of PKA and CaMKII and a Caveolin-3-knockout mouse model, we conclude that the β2AR-LTCC regulation requires the presence of caveolin-3 and the activation of the CaMKII pathway. (imperial.ac.uk)
  • Thus, CaMKII could decode compartmental dendritic Ca(2+) transients to support remodeling of local synapses. (nih.gov)
  • Activation of the LBD(G521R)-cNR2B transgenic protein in mice leads to the disruption of CaMKII/NR2B interactions at synapses. (caltech.edu)
  • Insulin stimulation generated partly independent signals leading to the rapid activation of Akt, Erk-1/2 and CaMKII Akt activation was followed by Glut-4 translocation to the plasma membrane and increase of glucose uptake. (cnr.it)
  • CaMKII activation is essential (22,23) and enough (24,25) for hippocampal NMDAR-dependent LTP, and CaMKII knockout (26C28) and knockdown (29) mice present serious deficits in?many learning duties. (healthyguide.info)
  • CaMKII is a molecule capable of affecting practically every facet of cellular metabolism and homeostasis upon activation, which depends on transiently elevated concentrations of calcium in the cell. (nlmfoundation.org)
  • Metabolic activation of CaMKII by coenzyme A. (umassmed.edu)
  • Moreover, this regulation relies on insulin gene expression through the activation of CaMKII and MafA. (lu.se)
  • The research has applications beyond understanding the molecular foundation of memory since CaMKII also is found in other calcium-coupled cells in the body, including cardiomyocytes in the heart and oocytes in the ovaries. (umass.edu)
  • There are four CaMKII isozymes, designated alpha, beta, gamma and delta, which may or may not be co-expressed in the same tissue type. (thermofisher.com)
  • In addition, shrinkage of the dentate gyrus occurs in the CaMKIIα-tTA activator line, although it is not yet known whether this is due to the expression of tTA or to the disruption of one or more endogenous mouse genes. (alzforum.org)
  • The CamKII-tTA transgene was designed by Dr. Mark Mayford (Columbia University, New York) with 8.5 kb of the mouse CaMKIIalpha promoter placed upstream of the tetracycline-regulated transactivator (tTA or "Tet-Off") gene (flanked by an artificial intron and splice sites at the 5' end and by a polyadenylation signal from SV40 at the 3' end). (mmrrc.org)
  • Transgene expression is largely restricted to the forebrain by the CaMKIIα promoter. (alzforum.org)
  • T2 mice were then crossed with the CaMKIIα-tTA activator line to create bi-transgenic mice (designated rT2/T2 when homozygous for the MAPT P301L transgene). (alzforum.org)
  • rTg4510 mice ("r" for regulatable) are produced by crossing the 4510 responder line, carrying a human MAPT P301L cDNA downstream of a tetracycline operon-responsive element (TRE), to an activator line expressing a tetracycline-controlled transactivator (tTA) under control of the CaMKIIα promoter. (alzforum.org)
  • While scientists have known for a while that CaMKII plays a critical role in normal cardiac function, ours is the first study to identify O-GlcNAc as a direct activator of CaMKII with hyperglycemia. (dentistrytoday.com)
  • buy 1619903-54-6 Indeed, there is certainly strong evidence that CaMKII plays a central function in synaptic memory and plasticity. (healthyguide.info)
  • Administering the gene therapy to mice just prior to the toxic insult (which initiates rapid damage to the cells), and just after optic nerve crush (which causes slower damage), increased CaMKII activity and robustly protected retinal ganglion cells. (newswise.com)
  • We provide evidence that KRas translocation occurs through sequestration of the polybasic-prenyl motif by Ca 2+ /calmodulin (Ca 2+ /CaM) and subsequent release of KRas from the PM, in a process reminiscent of GDP dissociation inhibitor-mediated membrane recycling of Rab and Rho GTPases. (rupress.org)
  • CaMKII alpha is autophosphorylated on Thr 286 upon the binding of the Ca2+/CaM complex to the autoinhibitory domain of CaMKII. (thermofisher.com)
  • Understanding the three-dimensional structure of the CaMKII molecule may be useful for understanding the way in which its function is carried out and for designing other molecules that can have a desirable physiological effect upon binding. (nlmfoundation.org)
  • CAMKII contains an N-terminal catalytic domain which binds ATP and substrate protein, regulatory domain (CBD) and association domain (ASD). (proteopedia.org)
  • Time-resolved DEER EPR and solid-state NMR afford kinetic and structural elucidation of substrate binding to Ca(2+)-ligated calmodulin. (nih.gov)
  • This comprehensive approach allowed Bers and his team to identify the specific site of sugar attachment to CaMKII, along with how that attachment activated CaMKII and caused calcium-dependent arrhythmias. (dentistrytoday.com)
  • Third, transiently turned on CaMKII can maintain steadily its activity over the proper buy 1619903-54-6 period span of many tests, and such decrease deactivation might take into account the few reviews of bistability in the books. (healthyguide.info)
  • And 4th, under in?vivo circumstances, boosts in phosphatase activity can easily boost CaMKII activity. (healthyguide.info)
  • CaMKII has important roles in regulating normal calcium levels, electrical activity, and pumping action of the heart, according to Bers. (dentistrytoday.com)
  • FRET-based sensor for CaMKII activity (FRESCA): A useful tool for assessing CaMKII activity in response to Ca2+ oscillations in live cells. (umassmed.edu)
  • Only HDAC4 binds strongly to CaMKII. (jci.org)
  • E ) IP of FLAG-HDAC4 deletion mutants coexpressed with Myc-CaMKIIδB-T287D to identify a domain of HDAC4 that binds to activated CaMKIIδB. (jci.org)
  • Calmodulin Interactions with Voltage-Gated Sodium Channels. (nih.gov)
  • These findings reveal a central role for HDAC4 in CaMKII signaling pathways and have implications for the control of gene expression by calcium signaling in a variety of cell types. (jci.org)
  • Subtype Differences in the Interaction of HIV-1 Matrix with Calmodulin: Implications for Biological Functions. (nih.gov)
  • Stratton and her team will use sequencing, biochemistry, structural biology and cellular assays to study the roles of CaMKII in different cells and how this one enzyme accommodates such multifunctionality. (umass.edu)
  • Yet the precise role of CaMKII in retinal ganglion cell health is not well understood. (newswise.com)
  • Given the abundance of CaMKII in the brain it has been proposed that CaMKII plays a key role in storage of information. (nlmfoundation.org)
  • Calmodulin Mutations in Human Disease. (nih.gov)
  • A ) Schematic representation of CaMKIIα domain arrangement (top). (elifesciences.org)
  • We have established ourselves as one of the laboratories leading this field and have available a unique combination of expertise and reagents in smooth muscle biology, Ca 2+ signaling and CaMKII structure-function that we bring to studies of vascular biology and pathophysiology and which we have made widely available to colleagues in the field. (amc.edu)
  • In summary, the present data suggest that deficits of BDNF levels and signaling through ERK1/2 and alpha-CaMKII might contribute to cognitive and neuroplastic defects associated with prenatal exposure to cannabinoids. (researchgate.net)
  • C ) COS cells were cotransfected with FLAG-pcDNA, -HDAC4, or -HDAC5 and Myc-CaMKIIδB-T287D. (jci.org)
  • In an additional experiment, the team found elevated levels of O-GlcNAc-modified CaMKII in both hearts and brains of deceased humans who were diagnosed with diabetes, with the highest levels in the hearts of patients who had both heart failure and diabetes. (dentistrytoday.com)
  • This localized and transient enrichment of CaMKII to dendritic sites coincided spatially and temporally with dendritic Ca(2+) transients. (nih.gov)
  • Only the activated form of CaMKIIδB physically interacted with HDAC4. (jci.org)
  • The American Heart Association, National Science Foundation, Fondation Leducq Transatlantic CaMKII Alliance, and the National Institutes of Health funded the study. (dentistrytoday.com)
  • Amino acids 529-657 were revealed to be required for cytosolic accumulation of HDAC4 in response to CaMKIIδB-T287D. (jci.org)