TY - JOUR. T1 - Mutational analysis of Ca2+-independent autophosphorylation of calcium/calmodulin-dependent protein kinase II. AU - Mukherji, Sucheta. AU - Soderling, Thomas. PY - 1995/6/9. Y1 - 1995/6/9. N2 - Previous studies with synthetic peptides indicate that residues 290-309, corresponding to the calmodulin (CaM)-binding domain of Ca2+/CaM-dependent protein kinase II interact with the catalytic core of the enzyme as a pseudosubstrate (Colbran, R. J., Smith, M. K., Schworer, C. M., Fong, Y. L., and Soderling, T. R. (1989) J. Biol. Chem. 264, 4800-4804). In the present study, we attempted to locate the pseudosubstrate motif by generation or removal of potential substrate recognition sequences (RXXS/T) at selected positions using site-directed mutagenesis. Based on previous results, Arg297, Thr305/306, and Ser314 were selected as key residues. Single mutations such as N294S, K300S, A302R, A309R, and R311A were expressed, purified, and characterized. Several of the mutants exhibited decreased ...
TY - JOUR. T1 - Identification of a Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in non-N-methyl-D-aspartate glutamate receptors. AU - Yakel, Jerrel L.. AU - Vissavajjhala, Prabhakar. AU - Derkach, Victor A.. AU - Brickey, Debra A.. AU - Soderling, Thomas R.. PY - 1995/2/28. Y1 - 1995/2/28. N2 - Glutamate receptor ion channels are colocalized in postsynaptic densities with Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II), which can phosphorylate and strongly enhance non-N-methyl-D-aspartate (NMDA) glutamate receptor current. In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. A synthetic peptide corresponding to residues 620-638 in GluR1 was phosphorylated in vitro by CaM-kinase II but not by cAMP-dependent protein kinase or protein kinase C. The 32P-labeled peptide map of this synthetic peptide appears to be the ...
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TY - JOUR. T1 - Amphetamine activate protein kinase C and calcium/calmodulin-dependent protein kinase via NMDA receptor in primary cultures of rat cortical neurons. AU - Wu, Hsueh-Hsia. AU - Lee, Horng-Mo. PY - 1999. Y1 - 1999. M3 - Article. VL - 1. SP - 12. EP - 19. JO - New Taipei Journal of Medicine. JF - New Taipei Journal of Medicine. SN - 1562-4242. ER - ...
Authors Affiliations: 1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Istituto di Endocrinologia e Oncologia Sperimentale del CNR Naples; 2Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples; 3Department of Medicine-DIMED, Unit of Endocrinology, University of Padua, Padova; and 4Department of Medicine and Surgery, University of Salerno, Salerno, ...
We investigated the effects of Wenxin Keli (WXKL) on the Calcium/Calmodulin dependent kinase II (CaMK II) signal transduction pathway with transverse aortic constriction (TAC) rats. Echocardiographic measurements were obtained 3 and 9 weeks after the surgery. Meanwhile, the action potentials (APDs) were recorded using the whole-cell patch clamp technique, and western blotting was used to assess components of the CaMK II signal transduction pathway. At both 3 and 9 weeks after treatment, the fractional shortening (FS%) increased in the WXKL group compared with the TAC group. The APD|sub|90|/sub| of the TAC group was longer than that of the Sham group and was markedly shortened by WXKL treatment. Western blotting results showed that the protein expressions of CaMK II, phospholamban (PLB), and ryanodine receptor 2 (RYR2) were not statistically significant among the different groups at both treatment time points. However, WXKL treatment decreased the protein level and phosphorylation of CaMK II (Thr
Secretoneurin, a Novel Endogenous CaMKII Inhibitor, Augments Cardiomyocyte Calcium Handling and Inhibits Arrhythmogenic Calcium ...
Greiser and colleagues (10) also report that, consistent with previous studies, the remaining RyR2 clusters were hyperphosphorylated at the protein kinase A (PKA) phosphorylation site (Ser2808), which may compensate for the reduction in RyR2 protein expression and help sustain subsarcolemmal Ca2+ release despite reduced L-type Ca2+ currents (Figure 1B). However, RAP myocytes exhibited reduced RyR2 phosphorylation at the calmodulin-dependent protein kinase II (CaMKII) phosphorylation site (Ser2815) and no changes in CaMKII activity. This finding contrasts with previous studies that reported increased atrial CaMKII activity and CaMKII-dependent RyR2-Ser2815 phosphorylation in human AF (5). Moreover, other studies have shown that treatment with CaMKII inhibitors or selective disruption of the Ser2815 CaMKII phosphorylation site prevented AF in animal models through a reduction of SR Ca2+ leak (12). One explanation for this discrepancy could be the limited duration of pacing in the rabbit model used ...
TY - JOUR. T1 - Persistent reversal of enhanced amphetamine intake by transient CaMKII inhibition. AU - Loweth, Jessica A.. AU - Li, Dongdong. AU - Cortright, James J.. AU - Wilke, Georgia. AU - Jeyifous, Okunola. AU - Neve, Rachael L.. AU - Bayer, K. Ulrich. AU - Vezina, Paul. PY - 2013/1/23. Y1 - 2013/1/23. N2 - Amphetamine exposure transiently increases Ca2+/calmodulin-dependent protein kinase II (CaMKII) α expression in the nucleus accumbens (NAcc) shell and this persistently increases local GluA1 S831 phosphorylation and enhances behavioral responding to the drug. Here we assessed whether transiently interfering with CaMKII signaling using a dominant-negative CaMKIIα mutant delivered to the NAcc shell with herpes simplex viral vectors could reverse these long-lasting biochemical and behavioral effects observed following exposure to amphetamine. As expected, transient expression of CaMKIIα K42M in the NAcc shell produced a corresponding transient increase in CaMKIIα and decrease in ...
Nuclear factor-kappa beta (NF-kβ) pro-inflammatory signalling is important in modulating endothelial dysfunction and may be important in vascular dysfunction associated with the ageing process. Recent studies in the heart have highlighted Calcium/calmodulin-dependent protein kinase II (CaMKII) as a novel regulator of NF-kβ signalling. However nothing is known of the role this interaction could play in regulating dysfunction of the vasculature during ageing. Here we (i) characterise NF-kβ signalling in vascular endothelial cells and examine the potential for CaMKII modulation and (ii) determine whether CaMKIIδ expression is altered in ageing.. Using human umbilical vein endothelial cells (HUVECs) as an in vitro model system, initial experiments have established that pro-inflammatory NF-kB signalling is activated in response to both tumour necrosis factor α (TNF-α) and interleukin-1β (IL-1β) stimulation. This was shown by a significant reduction in IkBα expression (1.18 ± 0.16 vs. 0.48 ...
Three genes encoding different Ca2+/calmodulin-dependent protein kinases have been characterized in the wheat phytopathogenic fungus Stagonospora nodorum. The kinases were identified from the S. nodorum genome sequence on the basis of sequence homology to known Ca2+/calmodulin- dependent protein kinases. Expression analysis determined that each of the kinases was expressed during growth in vitro and also during infection. The onset of sporulation triggered increased transcript levels of each of the kinases, particularly CpkA where an 11-fold increase in expression was observed during sporulation in planta. The role of the kinases was further determined via a reverse genetics approach. The disruption of CpkA affected vegetative growth in vitro and also sporulation. The cpkA strains produced 20-fold less spores on complex media and were unable to sporulate on defined minimal media. Infection assays showed that CpkA was not required for lesion development but was essential for sporulation at the ...
Rationale:: In the failing heart, persistent β-adrenergic receptor (βAR) activation is thought to induce myocyte death by protein kinase A (PKA)-dependent and PKA-independent activation of calcium/calmodulin-dependent kinase II (CaMKII) β-Adrenergic signaling pathways are also capable of activating cardioprotective mechanisms. Objective: This study used a novel PKA inhibitor peptide (PKI) to inhibit PKA activity to test the hypothesis that βAR signaling causes cell death through PKA-dependent pathways and cardioprotection through PKA-independent pathways. Methods and Results: In PKI transgenic mice, chronic isoproterenol (ISO) failed to induce cardiac hypertrophy, fibrosis, myocyte apoptosis and depressed cardiac function. In cultured adult feline ventricular myocytes (AFVMs), PKA inhibition protected myocytes from death induced byβ1-AR agonists by preventing cytosolic and SR Ca2+ overload and CaMKII activation. PKA inhibition revealed a cardioprotective role of β-adrenergic signaling via ...
Studies over the past decade have demonstrated that SR Ca2+ release is abnormal in patients with chronic AF.2 Whereas the amplitude of the L-type Ca2+ current is generally decreased in AF, Ca2+ leak through RyR2 is typically elevated despite similar or decreased SR Ca2+ contents.2,5 It has been proposed that triggered activity due to DADs is caused by an inward depolarizing INCX current, which occurs in response to the removal of excess Ca2+ release from the cytosol.9,10 We provide direct experimental evidence for this mechanism in the FKBP12.6−/− mouse model of AF. Our data revealed that FKBP12.6−/− mice exhibit atrial focal activity and AF caused by SR Ca2+ leak, NCX activation, and DADs generation. Because recent studies revealed that CaMKII phosphorylation of RyR2 at S2814 is elevated in patients with chronic AF,4,5 we investigated whether inhibition of S2814 phosphorylation of RyR2 affected susceptibility of FKBP12.6−/− to AF. Our results demonstrate that inhibition of S2814 but ...
Author Summary Memory is understood as strengthened synaptic connections among neurons. Paradoxically components of synaptic membranes are relatively short-lived and frequently re-cycled while memories can last a lifetime. This suggests synaptic information is encoded at a deeper, finer-grained scale of molecular information within post-synaptic neurons. Long-term memory requires genetic expression, protein synthesis, and delivery of new synaptic components. How are these changes guided on the molecular level? The calcium-calmodulin dependent protein kinase II (CaMKII) has been heavily implicated in the strengthening of active neural connections. CaMKII interacts with various substrates including microtubules (MTs). MTs maintain cellular structure, and facilitate cellular cargo transport, effectively controlling neural architecture. Memory formation requires reorientation of this network. Could CaMKII-MT interactions be the molecular level encoding required to orchestrate neural plasticity? Using
CAMK2A - CAMK2A (Myc-DDK-tagged)-Human calcium/calmodulin-dependent protein kinase II alpha (CAMK2A), transcript variant 2 available for purchase from OriGene - Your Gene Company.
CaMKII alpha antibody (calcium/calmodulin-dependent protein kinase II alpha) for ICC/IF, IHC-Fr, WB. Anti-CaMKII alpha pAb (GTX127939) is tested in Mouse, Rat samples. 100% Ab-Assurance.
Objectives:Sepsis is associated with cardiac contractile dysfunction attributed to alterations in Ca2+ handling. We examined the subcellular mechanisms involved in sarcoplasmic reticulum Ca2+ loss that mediate altered Ca2+ handling and contractile dysfunction associated with sepsis.Design:Randomized
Mouse eggs are ovulated following arrest at metaphase of the second meiotic division (metII). Fertilization breaks this arrest, with the egg extruding a second polar body (PB2) and forming pronuclei. Ca2+ spikes induced by phospholipase C zeta, which are introduced into the egg on gamete fusion, are responsible for causing the degradation of Erp1/Emi2 (Fbxo43 - Mouse Genome Informatics) (Ducibella and Fissore, 2008; Jones, 2005; Mehlmann, 2005; Swann et al., 2006). Erp1/Emi2 loss activates the anaphase-promoting complex (APC) and so drives exit from meiosis (Madgwick et al., 2006; Shoji et al., 2006).. In frog eggs, the Ca2+ fertilization signal switches on calmodulin-dependent protein kinase II (CamKII; Camk2), which phosphorylates Erp1/Emi2 and so promotes its degradation (Liu and Maller, 2005; Rauh et al., 2005; Schmidt et al., 2005). Consistent with this more recent development in the understanding of the molecular events of activation, it had been discovered several years previously, also ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Introduction: Glutamate excitotoxicity is an important mechanism of ischemic neuronal damage, however inhibition of glutamate receptors has proven an unsuccessful strategy. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major downstream target of glutamate signaling. The aim of this study is to examine the neuroprotective potential of inhibition of autonomous CaMKII activity using novel peptide inhibitors (tatCN21,19o) and transgenic mice.. Methods: C57BL/6 male wild-type (WT) and T286A mutant mice were subjected to 6 min of cardiac arrest and CPR. Mice were randomized to tatCN21 (1 mg/kg), tatCN19o (0.01,0.1,1 mg/kg) or control (tatSCR; 1 mg/kg), administered 30 min after CPR (iv). Separate experiments were performed to assess mild post-arrest hypothermia (rectal T = 34 ±0.2 °C for 1 hr after CPR). Hippocampal neuronal damage was analyzed 3 days after CA/CPR by H&E staining. Total CaMKII and Thr-286 phosphorylation levels were measured by western blot. Statistical analyses were ...
CAMK2B - CAMK2B (Myc-DDK-tagged)-Human calcium/calmodulin-dependent protein kinase II beta (CAMK2B), transcript variant 7 available for purchase from OriGene - Your Gene Company.
Anti-peptide antibodies specific for the neuronal calcium channel alpha 1E subunit (anti-CNE1 and anti-CNE2) were produced to study the biochemical properties and subcellular distribution of the alpha 1E polypeptide from rat brain. Immunoblotting identified a single size form of 245-255 kDa which was a substrate for phosphorylation by cAMP- dependent protein kinase, protein kinase C, cGMP-dependent protein kinase, and calcium/calmodulin-dependent protein kinase II. Ligand- binding studies of alpha 1E indicate that it is not a high affinity receptor for the dihydropyridine isradipine or the peptide toxins omega- conotoxin GVIA or omega-conotoxin MVIIC at concentrations which elicit high affinity binding to other channel types in the same membrane preparation. The alpha 1E subunit is widely distributed in the brain with the most prominent immunocytochemical staining in deep midline structures such as caudate-putamen, thalamus, hypothalamus, amygdala, cerebellum, and a variety of nuclei in the ...
Since its inception, the "synaptic tagging hypothesis" has inspired many to search for synaptic tags. However, very few molecules have been proposed as candidates (Frey and Frey, 2008). The nature and identity of PRPs and synaptic tags are under intensive investigations (Frey and Frey, 2008). Two pathway experiments showed that blockade of protein kinase A (PKA) or its interaction with A kinase-anchoring proteins (AKAPs) prevents synaptic capture, suggesting that PKA or its anchoring at active synapses may serve as a synaptic tag for L-LTP (Huang et al., 2006; Young et al., 2006). Calcium/calmodulin-dependent protein kinase II (CaMKII) is also implicated as an L-LTP-specific tag (Sajikumar et al., 2007). Studies thus far have been based on the use of pharmacological inhibitors in two-pathway experiments. However, it is necessary to show that these tags are transiently and locally activated in a protein synthesis-independent manner by weak stimulation. In a recent study, NMDA-dependent, ...
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The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory and cognition. The heterozygous CaMKIIα isoform KO (CaMKIIα+/-) mice have a schizophrenia-related phenotype, including impaired working memory. Here, we examined synaptic strength and plasticity in two brain areas implicated in working memory, hippocampus CA1 and medial prefrontal cortex (mPFC). Young CaMKIIα+/- mice (postnatal days 12-16; corresponding to a developmental stage well before schizophrenia manifestation in humans) showed impaired hippocampal CA1 LTP. However, this LTP impairment normalized over development and was no longer detected in older CaMKIIα+/- mice (postnatal weeks 9-11; corresponding to young adults). By contrast, the CaMKIIα+/- mice failed to show the developmental increase of basal synaptic transmission in the CA1 seen in wild-type (WT) mice, resulting in impaired basal
Complete information for CAMK4 gene (Protein Coding), Calcium/Calmodulin Dependent Protein Kinase IV, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
The concept of subcellular targeting by anchoring proteins is of major importance for understanding the specificity of signal transduction. The work presented here constitutes the first description of an anchoring protein for multifunctional CaM kinase II. αKAP exhibits three properties expected of anchoring proteins. (i) It is restricted to a specific cellular compartment, it is membrane bound and probably directly inserted into SR membranes by its N‐terminal hydrophobic domain (Figures 3 and 4). (ii) It binds CaM kinase II. This binding occurs within intact cells and not during extraction of transfected cells, since significant interaction was only detected after coexpression of αKAP and CaM kinase II, but not when individually expressed proteins were mixed (Figure 6). (iii) It is responsible for the targeting of the novel βM‐CaM kinase II to the SR, since it co‐immunoprecipitates with kinase extracted from SR membranes and the kinase does not have the physical properties of a ...
TY - JOUR. T1 - CaMKII inhibition in heart failure makes jump to human. AU - Bers, Donald M. PY - 2010/10/29. Y1 - 2010/10/29. KW - Ca transport. KW - Ca /calmodulin-dependent protein kinase. KW - heart failure. UR - http://www.scopus.com/inward/record.url?scp=78349273264&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=78349273264&partnerID=8YFLogxK. U2 - 10.1161/CIRCRESAHA.110.231902. DO - 10.1161/CIRCRESAHA.110.231902. M3 - Article. C2 - 21030721. AN - SCOPUS:78349273264. VL - 107. SP - 1044. EP - 1046. JO - Circulation Research. JF - Circulation Research. SN - 0009-7330. IS - 9. ER - ...
Lys-Lys-Lys-Leu-Arg-Arg-Gln-Glu-Ala-Phe-Asp-Ala-Tyr4374-v 0.5 mg | 90.00 EUR[Lys3, Phe10, Tyr13]-Autocamtide-2-Related Inhibitory Peptide ...
calmodulin-dependent protein kinase V: widely distributed in various tissues, involved in calcium-regulated processes; from rat brain; may exist in 40 & 41 kDa isoforms; amino acid sequence has been determined
The major finding of this study is that GIT1 is a novel mediator of Ang II-mediated VSMC gene transcription. Specifically we show that GIT1 participates in an Ang II signaling pathway that involves phosphorylation of HDAC5 and activation of MEF2, downstream of a pathway that requires Src, PLCγ, and CamK II (supplemental Figure V). Our results suggest that GIT1, via its multi-domain scaffolding function, coordinates Ang II signaling events that control calcium-dependent signaling (PLCγ and CamK II).. The focus of the present study is on CamK II which is a family of cytosolic serine/threonine protein kinases that exist as multimers consisting of α, β, δ, or γ subunits, each encoded by a different gene.24,25 Whereas CamK IIα and β are mainly expressed in neuronal tissues, CaMKIIδb, CaMKIIδc, and CaMKIIγ are abundant in the heart8,21,26 and VSMCs.27 CaMKII can phosphorylate type II HDACs.11 These HDACs (HDAC 4, 5, 7, and 9) normally repress transcriptional activity (eg, activation driven ...
Control of cardiomyocyte cytosolic Ca(2+) levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca(2+), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca(2+) channels/transporters. CaMKII is primarily expressed either in the δB or δC splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca(2+) levels promote the binding of a Ca(2+)/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post-translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post-translational modification status of CaMKIIδB/δC variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type ...
Wet-lab validated real-time PCR primer assays for your biological pathway of interest. Select your gene target of interest using an interactive pathway map, and select your plate.
SKF83959 is a high affinity dopamine D1 receptor agonist that has been reported to preferentially activate D1 receptors coupled to G(alpha)q. This pathway results in phosphatidylinositol hydrolysis, intracellular calcium mobilization, and potential activation of Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIalpha), an important regulator of synaptic transmission. Although the exact mechanism remains unclear, one recent model suggested that SKF83959 activates a D1/D2 receptor heteromer complex coupled to G(alpha)q. Here, we have used genetic models to define the signaling specificity of SKF83959 using behavioral endpoints. Furthermore, we have extended the behavioral characterization of SKF83959 on motor output and additionally defined SKF83959-induced effects on anxiety and depressive-like behaviors. In wildtype mice, a peripheral injection of SKF83959 (1mg/kg) produced a modest but significant increase in horizontal locomotor activity and orofacial grooming. The SKF83959-induced ...
Camk2d2 antibody (calcium/calmodulin-dependent protein kinase (CaM kinase) II delta 2) for IHC-P, WB. Anti-Camk2d2 pAb (GTX124377) is tested in Zebrafish samples. 100% Ab-Assurance.
Previous work has shown that neurotrophins rapidly potentiate synaptic transmission through presynaptic mechanisms. The acute potentiation of transmitter release by BDNF is accompanied by a rise in [Ca2+]i in both the NMJ (Stoop and Poo 1995) and at the CNS synapses (Berninger and Garcia 1993; Marsh and Palfrey 1996; Sakai et al. 1997; Li et al. 1998). However, it is unclear whether and how the increase in [Ca2+]i mediates the neurotrophin-induced synaptic potentiation and which downstream signaling events are involved. In this paper we report a surprising finding that the acute potentiation of transmitter release by NT3 at the neuromuscular synapses is independent of Ca2+ influx from extracellular sources. Instead, this potentiation is mediated by Ca2+ released from intracellular stores through IP3 and ryanodine receptors. Thus, the mechanisms by which BDNF and NT3 modulate transmitter release could be quite different. Furthermore, we demonstrated that Ca2+ released from intracellular stores is ...
Calcium and calmodulin-dependent protein kinase II (CaMKII) plays a fundamental role in the synaptic plasticity events that underlie learning and memory. Regulation of CaMKII kinase activity occurs through an autoinhibitory mechanism in which a regulatory domain of the kinase occupies the catalytic site and calcium/calmodulin activates the kinase by binding to and displacing this regulatory domain. A single putative ortholog of CaMKII, encoded by unc-43, is present in the Caenorhabditis elegans nervous system. Here we examined UNC-43 subcellular localization in the neurons of intact animals and show that UNC-43 is localized to clusters in ventral cord neurites, as well as to an unlocalized pool within these neurites. A mutation that mimics autophosphorylation within the regulatory domain results in an increase in the levels of UNC-43 in the unlocalized neurite pool. Multiple residues of CaMKII facilitate the interaction between the catalytic domain and the regulatory domain, thereby keeping the ...
Previous studies indicate that LTP induction increases the CaMKII-dependent phosphorylation of GluR1 at Ser831. Although such phosphorylaton may enhance the function of synaptic receptors, this phosphorylation does not seem to be required for receptor delivery: tCaMKII can deliver GluR1(S831A)-GFP to the synapse. Our results indicate that some protein(s) other than GluR1 must be substrate(s) of CaMKII (Choquet: Stargazin) and participate in the regulated synaptic delivery of AMPARs ...
FUNCTION: ACTIVATES TYROSINE AND TRYPTOPHAN HYDROXYLASES IN THE PRESENCE OF CA(2+)/CALMODULIN-DEPENDENT PROTEIN KINASE II, AND STRONGLY ACTIVATES PROTEIN KINASE C. IS PROBABLY A MULTIFUNCTIONAL REGULATOR OF THE CELL SIGNALING PROCESSES MEDIATED BY BOTH KINASES ...
Association of NCAM140 with lipid rafts is required for CaMKIIα activation. (A, left) Representative images of neurites of cultured hippocampal neurons treated
Usled njihove sposobnosti da se autofosforilišu, CaMK aktivnost može da bude dugotrajnija od intracelularnog kalcijuma koji je neophodan za njihovu aktivaciju. U neuronima, ova osobina je važna za indukciju sinaptičke plastičnosti.[2] Farmakološka inhibicija CaMKII blokira indukciju dugotrajne potencijacije. Nakon aktivacije, CaMKII fosforiliše postsinaptičke glutamatne receptore i time menja električne osobine sinapse.. ...
Looking for online definition of CaM kinase II delta subunit in the Medical Dictionary? CaM kinase II delta subunit explanation free. What is CaM kinase II delta subunit? Meaning of CaM kinase II delta subunit medical term. What does CaM kinase II delta subunit mean?
Excessive activation of β-adrenergic, angiotensin II, and aldosterone signaling pathways promotes mortality after myocardial infarction (MI), while antagonist drugs targeting these pathways are core therapies for treating post-MI patients. The multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is activated by catecholamines and angiotensin II, and CaMKII inhibition prevents isoproterenol- and angiotensin II-mediated cardiomyopathy. Here we ask the hypothesis if aldosterone and CaMKII participated in common responses to MI by developing a mouse MI model supplemented by aldosterone infusion (MI+Aldo) to approximate plasma aldosterone levels measured in MI patients. We find that aldosterone exerts direct toxic actions on myocardium by oxidative activation of CaMKII, causing cardiac rupture and increased mortality in mice after MI (65.5% for aldosterone versus 31.0% for vehicle, P=0.007, n≥19 mice per treatment). Aldosterone oxidizes CaMKII by recruiting NADPH oxidase, and ...
Our data show that LTP inducing stimulation produces a 6-fold increase in endogenous synapsin I phosphorylation at its CaM kinase II sites. The observed rise in synapsin I phosphorylation occurred rapidly after the stimulation and persisted for at least 30 min. Most importantly, this effect was not observed in the presence of the NMDA receptor antagonist APV, suggesting that the rise in synapsin I phosphorylation is due to the LTP-inducing nature of the stimulation. Since synapsin I is localized exclusively in the presynaptic terminal, our data provide strong evidence that LTP expression is accompanied by persistent biochemical changes in the presynaptic terminal. Because the observed LTP-associated presynaptic changes require NMDA receptor activation, these data support models of LTP in which a retrograde messenger (generated subsequent to postsynaptic NMDA receptor activation) may produce presynaptic changes underlying LTP (36-38).. The mechanism by which LTP induction might lead to this ...
Introduction: The calcium/calmodulin-dependent kinase II (CaMKII) is activated by angiotensin-II, a strong inducer of vascular smooth muscle cell (VSM) hypertrophy. CaMKII activates HDAC4/MEF-2 dependent gene transcription by phosphorylation of HDAC4 S467 and 632. Here, we demonstrate that CaMKII mediates Ang-II-induced VSM hypertrophy in vitro and in vivo by activation of the HDAC4/MEF-2 signal transduction pathway.. Methods and Results: Medial hypertrophy by Ang-II infusion at pressor dose over 10 days was significantly reduced in C57Bl/6 mice when the CaMKII inhibitor KN93 was given daily i.p. (0.070 mm2 vs 0.052 mm2, p,0.05). In vitro, Ang-II increased the 3H-Leucine/3H-Thymidine uptake in control aortic VSM cells by 50% after 24 hr, whereas overexpression of the CaMKII peptide inhibitor CaMKIIN resulted only in 14 % increase (p,0.05). Ang-II induced phosphorylation of HDAC4 that was further increased under overexpression of CaMKIIδ2. CaMKII overexpression resulted in increased ...
Raval A, Tanner SM, Byrd JC, Angerman EB, Perko JD, Chen SS, Hackanson B, Grever MR, Lucas DM, Matkovic JJ, Lin TS, Kipps TJ, Murray F, Weisenburger D, Sanger W, Lynch J, Watson P, Jansen M, Yoshinaga Y, Rosenquist R, de Jong PJ, Coggill P, Beck S, Lynch H, de la Chapelle A, Plass C. Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia. Cell. 2007 Jun 01; 129(5):879-90 ...
Small molecule inhibitors of the human sirtuins and calmodulin-dependent protein kinases have shown promising anti-cancer activity in cell-based screens and animal models. We have synthesized analogues of these compounds, identifying more selective sirtuin inhibitors and more potent calmodulin-dependent protein kinase inhibitors.The sirtuins are a family of NAD+-dependent deacetylases that regulate cellular aging and gene silencing in simple organisms and appear to play important regulatory roles in human cells that make them attractive anti-cancer targets. We have previously identified the compound cambinol, an inhibitor of the human sirtuins SIRT1 and SIRT2, which is selectively toxic to Burkitts lymphoma cells. In order to determine which sirtuin is the relevant target, we screened analogues of cambinol, identifying compounds that exhibited moderate selectivity for both SIRT1 and SIRT2. The compound JP136 is ten-fold more selective in vitro for SIRT1 over SIRT2, with respective IC50s of 13 ...
This invention relates to the controlled release of calcium sulfate as well as to the controlled release of an additive to a calcium sulfate matrix such as medicaments or pesticides. The controlled release is achieved by a pellet comprising calcium sulfate. The pellet is prepared by the process comprising mixing powder consisting essentially of alpha-calcium sulfate hemihydrate, a solution comprising water, and, optionally, an additive and a powder consisting essentially of beta-calcium sulfate hemihydrate to form a mixture, and forming said mixture into a pellet, wherein said alpha-calcium sulfate hemihydrate and beta-calcium sulfate hemihydrate powders have specified properties such as BET surface areas, densities, mean particle sizes, and purifies. The dissolution rate of the calcium sulfate pellet is controlled by varying the weight ratio of the beta-calcium sulfate hemihydrate powder to the alpha-calcium sulfate hemihydrate powder from 0 to about 3. The invention also provides a method of
0071] The peptide hormone Ang II induces opening of mitochondrial KATP channels, depolarizes ΔΨm, and amplifies ROS generation from mitochondria [46]. We have shown that inhibition of CaMKII can protect against Ang II induced ROS species generation (FIG. 6). H9C2 cells and eventually neonatal cardiomyocytes from WT and mitoCaMKIIN mice will be cultured as described above, and peptide-loaded PLGA/PAMAM nanoparticles with and without surface bound MLS ligands will be prepared as described above. Cells will be treated with Ang II (1 μM for 3 hours). Both H9C2 cells and neonatal cardiomyocytes will be tested. We plan to isolate cardiomyocytes from four mouse litters of mitoCaMKIIN mice. Because these transgenic mice are crossed to WT-C57 mice each generation, the WT littermates will be used to test treated and untreated nanoparticles. A series of increasing doses of nanoparticles will be co-incubated with Ang II to determine the dose-response curve for generating protection against changes ...