Trouvez tous les livres de Stenmark, Harald (ed.) - Phosphoinositides in Subcellular Targeting and Enzyme Activation. Sur eurolivre.fr,vous pouvez commander des livres anciens et neufs.COMPARER ET acheter IMMÉDIATEMENT au meilleur prix. 9783540009504
Brajendra K. Tripathi, View ORCID ProfileTiera Grant, Xiaolan Qian, Ming Zhou, Philipp Mertins, Dunrui Wang, Alex G. Papageorge, View ORCID ProfileSergey G. Tarasov, View ORCID ProfileKent W. Hunter, Steven A. Carr, View ORCID ProfileDouglas R. Lowy ...
Rabbit polyclonal BCKDH kinase antibody validated for WB, IHC and tested in Human and Mouse. Referenced in 1 publication. Immunogen corresponding to…
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Elevated levels of the sIL-6R have been associated with the pathology of several disease states. This implies that production of the sIL-6R is increased as part of the inflammatory response. However, little is known regarding the factors that might regulate sIL-6R generation. In this study, physiological concentrations of native CRP and biologically relevant CRP-derived peptides were found to stimulate sIL-6R production by human neutrophils. Release of this soluble receptor was rapidly induced after CRP treatment and occurred via shedding of the cognate IL-6R from the cell surface. C-reactive protein represents the first known endogenous activator of this process. The observation that release of sIL-6R is only partially prevented by the hydroxamic acid-based metalloprotease inhibitor TAPI is of particular interest, since IL-6R shedding in response to phorbol esters and ionomycin has been shown to be prevented by this agent ((12), (20)). Thus, in neutrophils, shedding of the IL-6R presumably ...
Absence of adequate regulation is a prerequisite for pathophysiological developments, like hypersensitivity reactions and cancer. Thus, comprehension of physiological reactions requires knowledge about their regulation. In previous years, we were able to work out the central role which is played by the inositol-5-phosphatase, SHIP1, in regulating appropriate mast cell (MC) responses. If SHIP1 is missing, MCs severely hyper-react in response to diverse stimuli, like allergens, growth factors, and bacterial constituents. So far, this cellular behavior was explained mainly by SHIP1s catalytic function. However, in addition to its catalytic domain SHIP1 possesses various structural possibilities to interact with other proteins (i. e. an adaptor function). To understand how SHIP1 is controlling the physiological activation of MCs and why SHIP1 deficiency is resulting in hyperreactivity of MCs, we will, in this proposed project, thoroughly analyze the structural characteristics of SHIP1 and correlate ...
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Activation results during learning (Day 1).A: JULIDE results. At Day 1, the hippocampus (HP) and the parietal associative cortex (PTLp) are the most activated r
Protein kinase C regulates the activity of a diverse group of cellular proteins including membrane ion channel proteins. Although protein kinase C and its substrate protein have been identified in both membrane and cytosolic fractions in the heart, the physiological role of this kinase in the regulation of cardiac function remains unknown. We examined the physiological role of protein kinase C by stimulating its activity with 12-deoxyphorbol 13 isobutyrate 20 acetate (DPBA) in human trabeculae carneae. This resulted in decreased peak isometric twitch force and peak intracellular sarcoplasmic reticulum calcium release as detected with aequorin. Furthermore, in the presence of DPBA, steady-state force-[Ca2+] relations were shifted to higher intracellular calcium concentrations, and the Hill coefficient was reduced, indicating a decrease in responsiveness of the myofilaments to calcium and a change in cooperativity among thin filament proteins, respectively. Thus, DPBA affects not only ...
Stress-activated protein kinases (SAPKs) are stimulated by cell damaging agents as well as by physiological receptor agonists. In this study we show that human platelets contain the isoforms SAPK2a, SAPK2b, SAPK3 and SAPK4 as determined by immunoblotting with specific antibodies. All four kinases were activated in thrombin-stimulated platelets whereas only SAPK2a and SAPK2b were significantly stimulated by collagen. All four isoforms were able to phosphorylate wild-type human cPLA2in vitro, although to different extents, but not cPLA2 mutants that had Ser505 replaced by alanine. Phosphorylation at Ser505 was confirmed by phosphopeptide mapping using microbore HPLC. SAPK2a and 42-kDa mitogen-activated protein kinase incorporated similar levels of phosphate into cPLA2 relative to the ability of each kinase to stimulate phosphorylation of myelin basic protein. SAPK2b and SAPK4 incorporated less phosphate, and cPLA2 was a poor substrate for SAPK3. The inhibitor of SAPK2a and SAPK2b, SB 202190, ...
Maudsley S., Pierce K.L., Zamah A.M., Miller W.E., Ahn S., Daaka Y., Lefkowitz R.J., Luttrell L.M.. Many G protein-coupled receptors (GPCRs) activate MAP kinases by stimulating tyrosine kinase signaling cascades. In some systems, GPCRs stimulate tyrosine phosphorylation by inducing the "transactivation" of a receptor tyrosine kinase (RTK). The mechanisms underlying GPCR-induced RTK transactivation have not been clearly defined. Here we report that GPCR activation mimics growth factor-mediated stimulation of the epidermal growth factor receptor (EGFR) with respect to many facets of RTK function. beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization, tyrosine autophosphorylation, and EGFR internalization. Coincident with EGFR transactivation, isoproterenol exposure induces the formation of a multireceptor complex containing both the beta(2)AR and the "transactivated" EGFR. beta(2)AR-mediated EGFR phosphorylation and subsequent beta(2)AR stimulation of ...
One of the key mediators of the antiviral and antiproliferative actions of interferon is double-stranded-RNA-dependent protein kinase (PKR). PKR activity is also involved in the regulation of cell proliferation, apoptosis and signal transduction. We have recently identified PACT, a novel protein activator of PKR, as an important modulator of PKR activity in cells in the absence of viral infection. PACT heterodimerizes with PKR and activates it by direct protein-protein interactions. Endogenous PACT acts as an activator of PKR in response to diverse stress signals, such as serum starvation and peroxide or arsenite treatment, and is therefore a novel, stress-modulated physiological activator of PKR. In this study, we have characterized the functional domains of PACT that are required for PKR activation. Our results have shown that, unlike the N-terminal conserved domains 1 and 2, the third conserved domain of PACT is dispensable for its binding of double-stranded RNA and inter action with PKR. ...
The data reported herein show the capacity of NSC 651016 to act as an inhibitor of CXCL12-mediated angiogenesis in a variety of in vitro and in vivo angiogenesis assays. Furthermore, these data suggest the potential application of NSC 651016 as an antiangiogenic therapy because it blocked endothelial cell migration, capillary-like tube formation, and angiogenesis. Furthermore, NSC 651016 may have wider applications in cancer therapy. CXCL12 has been implicated in the proliferation of astrocytes (14) by activating extracellular signal-regulated kinase 1/2 but not p38 or stress-activated protein kinase/c-Jun NH2-terminal kinase pathways (14) , therefore, CXCL12 may have a direct role in pathological glial cell proliferation such as reactive gliosis and brain tumor formation. Thus, blockade of CXCL12 function by NSC 651016 may have direct therapeutic benefits for certain brain cancers, one of the most refractory tumor types known. Additionally, CXCL12 participates in cancer cell metastasis by ...
p,This chapter presents a general approach for the application of spatial intensity distribution analysis (SpIDA) to the pharmacodynamic quantification of receptor tyrosine kinase homodimerization in response to direct ligand activation or transactivation by G-protein-coupled receptors. Intensity histograms are generated from single fluorescence microscopy images. These histograms are then fit with Poissonian distributions to obtain density maps and quantal brightness values of the labeled proteins underlying the images. This approach allows resolving monomer/oligomer protein mixtures within subcellular compartments using conventional confocal laser scanning microscopy. The application of quantitative pharmacological analysis to data obtained using SpIDA provides a universal method for comparing studies between cell lines and receptor systems. In contrast to methods based on resonance energy transfer, SpIDA is suitable not only for use in recombinant systems but also for the characterization of ...
Concepts regarding the controls and consequences of PKD1-Ser738/Ser742 (activation loop) phosphorylation are based largely on early studies that used an anti-PKD1-Ser(P)738/Ser(P)742 PSSA (from Cell Signaling Technology, Danvers, MA) and showed that PMA increases PKD1 activation loop phosphorylation in many cell types via a mechanism that requires nPKC isoform activity (PKCδ, PKCε, PKCη, and/or PKCθ). In vitro kinase assays showing direct phosphorylation of the PKD1 activation loop by certain nPKC isoforms also have been published (Brändlin et al., 2002). However, there is recent evidence that the Cell Signaling Technology anti-PKD1-Ser(P)738/Ser(P)742 PSSA primarily recognizes PKD1 phosphorylation at Ser738 and that PKD1 phosphorylation at Ser742 can be tracked with a different PSSA (commercially available from Abcam Inc., Cambridge, MA). Experiments that use a combined approach with these two PSSAs expose differences in the controls and consequences of PKD1 phosphorylation at Ser738 and ...
Sprouty-related, EVH1 domain-containing protein 3 also known as Spread-3 is a protein that in humans is encoded by the SPRED3 gene. Spread-3 is a member of the Sprouty (see SPRY1/SPRED) family of proteins that regulate growth factor-induced activation of the MAP kinase cascade. GRCh38: Ensembl release 89: ENSG00000188766 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000037239 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: sprouty-related". Nonami A, Kato R, Taniguchi K, Yoshiga D, Taketomi T, Fukuyama S, Harada M, Sasaki A, Yoshimura A (December 2004). "Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells". The Journal of Biological Chemistry. 279 (50): 52543-51. doi:10.1074/jbc.M405189200. PMID 15465815. Kato R, Nonami A, Taketomi T, Wakioka T, Kuroiwa A, Matsuda Y, Yoshimura A (March 2003). "Molecular cloning of mammalian Spred-3 which suppresses tyrosine ...
Glycerol kinase antibody [N1N3-2] (glycerol kinase) for ICC/IF, WB. Anti-Glycerol kinase pAb (GTX107474) is tested in Human samples. 100% Ab-Assurance.
Many stimuli mediate activation and nuclear translocation of ERK (extracellular-signal-regulated kinase) by phosphorylation on the TEY (Thr-Glu-Tyr) motif. This is necessary to initiate transcriptional programmes controlling cellular responses, but the mechanisms that govern ERK nuclear targeting are unclear. Single-cell imaging approaches have done much to increase our understanding of input-output relationships in the ERK cascade, but few studies have addressed how the range of ERK phosphorylation responses observed in cell populations influences subcellular localization. Using automated microscopy to explore ERK regulation in single adherent cells, we find that nuclear localization responses increase in proportion to stimulus level, but not the level of TEY phosphorylation. This phosphorylation-unattributable nuclear localization response occurs in the presence of tyrosine phosphatase and protein synthesis inhibitors. It is also seen with a catalytically inactive ERK2-GFP (green fluorescent ...
It has been suggested that S100A8 acts as an endogenous activator of the immune response (6). S100A8 expression is strongly upregulated in various inflammatory diseases, such as sepsis, rheumatoid arthritis, inflammatory bowel disease, vasculitis, and cancer (5). NAFLD has been increasingly recognized as an inflammatory disease as well as a metabolic disease (4). However, the involvement of S100A8 in the pathogenesis of NAFLD remains unclear. In the current study, we demonstrated that S100A8 expression was remarkably increased in the livers of HFHCD-fed mice that developed steatohepatitis. We also demonstrated that S100A8 protein was significantly more expressed in the liver tissues of patients with NASH than in those of patients with NAFL. These results suggested that S100A8 was associated with the development of NAFLD. Furthermore, we demonstrated that S100A8 was primarily produced in the myeloid lineage cell population, CD11b+Gr-1high cells in the liver leukocytes of both ND- and HFHCD-fed ...
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Separation of the catalytic and stimulatory regulatory subunits of rat brain adenylate cyclase.: The catalytic subunit of rat brain adenylate cyclase was separa
Sigma-Aldrich offers abstracts and full-text articles by [Shinichi Meguro, Noriko Osaki, Koji Onizawa, Noriyuki Yajima, Tadashi Hase, Noboru Matsuo, Ichiro Tokimitsu].
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In pyroptosis experiments, nigericin can be used as a positive control to generate a robust caspase-1 activation response in a variety of cell lines.
To demon selleckchem strate irrespective of whether ET 1 stimulates ERK1 two, p38 MAPK, and JNK1 2 phosphorylation via a G protein coupled ETB re ceptor cascade, pretreatment with BQ 788, GPA2, or GPA2A attenuated ET 1 stimulated ERK1 2, p38 MAPK, and JNK1 two phosphorylation through the period of observation. These results demonstrated that G protein coupled ETB dependent activation of ERK1 2, p38 MAPK, and JNK1 2 by ET 1 is, at the least in part, needed for COX two expression in bEnd. 3 cells. NFB is required for ET 1 induced COX two expression ET 1 has been shown to modulate cellular functions via activation of NFB signaling in a variety of cell sorts. To examine no matter whether activation of NFB is essential for ET 1 induced COX 2 expression, as shown in Figure 5A and B, pretreatment with a selective NFB inhibitor Bay11 7082, which blocks activation of NFB signaling, attenuated ET 1 induced COX 2 protein and mRNA expression in bEnd. three cells. To figure out whether or not the involvement ...
Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12-myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester-resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phenotype were examined, using a newly-established resistant cell line. Phorbol ester induced morphological changes, ERK activation, calcium-dependent activation of the c-Jun N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in sensitive but not resistant cells. A series of protein kinase C activators caused membrane translocation of protein kinase Cs (PKCs) alpha, eta, and theta in both cell lines. While PKC eta was expressed at higher levels in sensitive than in resistant cells, overexpression of PKC eta did not restore phorbol ester-induced ERK activation to resistant cells. In sensitive cells, PKC activators had similar effects on cell viability and ERK ...
Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signal-regulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a ...
G-protein-coupled receptor agonists are powerful stimulators of mitogen-activated protein kinase (MAPK) cascades in cardiac myocytes. However, little is known regarding the physiological activation of enzymes downstream of MAPKs. We examined the activation of mitogen- and stress-activated protein kinase-1 (MSK1), a downstream target of MAPKs, in adult rat cardiac myocytes by phenylephrine and endothelin-1. Both agonists induced the phosphorylation of MSK1 at Thr-581 and Ser-376 but not at Ser-360. Maximal phosphorylation was observed at 10-15min after stimulation and it correlated with increased activity. Maximal activation of MSK1 in adult cardiomyocytes temporally coincided with maximal p38 MAPK activation while activation of the extracellular-signal-regulated kinase (ERK) cascade was more rapid. Phosphorylation and activation of MSK1 was completely inhibited by either PD98059 (ERK1/2 pathway inhibitor) or SB203580 (p38 MAPK inhibitor) alone. These data demonstrate that MSK1 activation in ...
Phagocyte superoxide production by a multicomponent NADPH oxidase is important in host defense against microbial invasion. However inappropriate NADPH oxidase activation causes inflammation. Endothelial cells express NADPH oxidase and endothelial oxidative stress due to prolonged NADPH oxidase activation predisposes many diseases. Discovering the mechanism of NADPH oxidase activation is essential for developing novel treatment of these diseases. The p47(phox) is a key regulatory subunit of NADPH oxidase; however, due to the lack of full protein structural information, the mechanistic insight of p47(phox) phosphorylation in NADPH oxidase activation remains incomplete. Based on crystal structures of three functional domains, we generated a computational structural model of the full p47(phox) protein. Using a combination of in silico phosphorylation, molecular dynamics simulation and protein/protein docking, we discovered that the C-terminal tail of p47(phox) is critical for stabilizing its ...
H2O2 and oxygen-derived free radicals modulate vasodilator mechanisms.1 2 3 4 5 6 9 The present studies indicate that H2O2 enhances adenylyl cyclase activation and that the effect is dependent (in part) on the presence of iron and is blunted by agents that act to inhibit tyrosine kinase activity.. Our data suggest that the oxygen-derived species mediating the enhancement of adenylyl cyclase activation is either H2O2 itself or the hydroxyl radical. Incubation of cells with xanthine oxidase and purine resulted in a qualitatively similar enhancement of adenylyl cyclase activation. The effect of purine and xanthine oxidase was not blocked by coincubation with superoxide dismutase (which catalyzes the conversion from superoxide anion to H2O2). This suggests that the generation of the superoxide anion is not involved in the mechanism of enhancement of adenylyl cyclase activation. However, pretreatment with either catalase (which catalyzes conversion of H2O2 to water) or with deferoxamine (which ...
TY - JOUR. T1 - Stimulation of Jun N-terminal kinase (JNK) by gonadotropin-releasing hormone in pituitary αt3-1 cell line is mediated by protein kinase C, c-Src, and CDC42. AU - Levi, N. L.. AU - Hanoch, T.. AU - Benard, Outhiriaradjou. AU - Rozenblat, M.. AU - Harris, D.. AU - Reiss, N.. AU - Naor, Z.. AU - Seger, R.. PY - 1998. Y1 - 1998. N2 - The signaling of ligands operating via heterotrimeric G proteins is mediated by a complex network that involves sequential phosphorylation events. Signaling by the G protein-coupled receptor GnRH was shown to include elevation of Ca2+ and activation of phospholipases, protein kinase C (PKC) and extracellular signal-regulated kinase (ERK). In this study, GnRH was shown to activate Jun N-Terminal Kinase (JNK)/SAPK in αT3-1 cells in a PKC- and tyrosine kinase-dependent manner. GnRH as well as tumor-promoting agent (TPA) also increased c-Src activity, which peaked at 2 min after GnRH stimulation and was sensitive both to PKC and to tyrosine kinase ...
TY - JOUR. T1 - Role of EGF receptor and Pyk2 in endothelin-1-induced ERK activation in rat cardiomyocytes. AU - Kodama, Hiroaki. AU - Fukuda, Keiichi. AU - Takahashi, Toshiyuki. AU - Sano, Motoaki. AU - Kato, Takahiro. AU - Tahara, Satoko. AU - Hakuno, Daihiko. AU - Sato, Toshihiko. AU - Manabe, Tomohiro. AU - Konishi, Fusako. AU - Ogawa, Satoshi. PY - 2002/2/1. Y1 - 2002/2/1. N2 - G protein-coupled receptor (GPCR)-evoked signal transduction pathways leading to the activation of extracellular signal-regulated kinases (ERK) are quite different among cell types. In cardiomyocytes, much attention has been focused on the activation of protein kinase C (PKC) or mobilization of intracellular Ca2+ ([Ca2+]i), however, the contributions of tyrosine kinases are controversial. In the present study, we characterized the signaling pathways involving tyrosine kinases, Pyk2 and epidermal growth factor receptor (EGFR), and their contribution to ERK activation in cultured cardiomyocytes. We initially ...
Global Markets Directs, Protein Kinase C Epsilon Type (nPKC Epsilon or PRKCE or EC 2.7.11.13) - Pipeline Review, provides in depth analysis on Protein Kinase C Epsilon Type (nPKC Epsilon or PRKCE or EC 2.7.11.13) targeted pipeline therapeutics.
Although accumulating evidence supports that JNK activation is involved in cancer development and progression [37, 38], the biological significance of JNK in gastric cancer remains unclear. The present study showed that constitutive activation of JNK was associated with specific clinicopathological factors, including pTNM stages, lymphatic invasion, and a better prognosis. We believe that this is the first report regarding the clinical implications of JNK in human gastric cancer. Furthermore, we found that JNK negatively regulates FOXO1 activation in gastric cancer cells. This finding contrasts with the results of the previous studies [22, 27-31], which showed JNK-induced activation of FOXO proteins in human cancer cells.. In the present study, JNK activation (evaluated by pJNK staining) was mainly observed in the proliferative zone of the gastric gland and in the areas showing intestinal metaplasia, which is known to be a predictor of gastric neoplasia [39], in the non-neoplastic gastric ...
We found that removal of Ca2+ and inhibition of PKC prevented high Pi-induced O2·− production (Figures 3A and 3B), indicating a role for mechanosensitive Ca2+ signaling and PKC-dependent pathways in high Pi-induced upregulation of NAD(P)H oxidase activity. This idea is consistent with the findings that high Pi elicited significantly greater increases in smooth muscle [Ca2+]i than normal levels of Pi (Figure 4). The important role of Ca2+ signaling is also supported by the finding that administration of a Ca2+ ionophore resulted in significantly increased arterial O2·− production (Figure 3C). Further, pharmacological activation of PKC2 elicited substantial increases in arterial NAD(P)H oxidase-derived O2·− generation (Figure 3C). Because removal of Ca2+ during high-pressure treatment prevented endothelial dysfunction (Figure 1) and increases in O2·− production in high Pi-exposed arteries (Figure 3A) and phorbol ester-stimulated O2·− generation in normotensive arteries could also be ...
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What cellular and molecular properties of neurons in the T-SWR support a 45 min spacing interval for two-trial LTM? Studies of the patterning requirements for the induction of long-term facilitation (LTF) of the tail SN-motor neuron (MN) synapse parallel those for sensitization memory in the T-SWR (Mauelshagen et al., 1996, 1998). For example, four spaced (ISI of 15 min) pulses of exogenous 5-HT are required to induce LTF at tail SN-MN synapses (Mauelshagen et al., 1996). If 5-HT release within the CNS is a critical signaling event initiated by TS, an important experimental question is whether two spaced 5-HT pulses (ISI of 45 min) can induce LTF or whether additional 5-HT signaling (provided by additional pulses) is required.. The analysis of repeated trial learning in Aplysia has identified several critical molecular requirements for LTM induction downstream of 5-HT. These include the signaling kinases protein kinase A (PKA), MAPK, the transcription factor CREB1, and CRE-mediated transcription ...
The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection-activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr) mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic
View mouse Mapkapk5 Chr5:121525038-121545905 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Protein Kinase C Theta Type (nPKC Theta or PRKCQ or EC 2.7.11.13) - Pipeline Review, H1 2017 Size and Share Published in 2017-05-30 Available for US$ 3500 at Researchmoz.us
MAPK3 [ENSP00000263025]. Extracellular signal-regulated kinase 1; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are ...
Rabbit recombinant monoclonal Myosin light chain kinase antibody [EP1458Y] validated for WB, IHC, Flow Cyt, ICC/IF and tested in Human, Mouse and Rat…
PubMed journal article Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasi were found in PRIME PubMed. Download Prime PubMed App to iPhone or iPad.
|p|GF 109203X is a potent and selective inhibitor of protein kinase C [1].|/p||p| Protein kinase C (PKC) is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of serine and threon
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to
Phosphorylation of mitogen-activated protein kinases (MAPKs) on specific tyrosine and threonine sites by MAP kinase kinases (MAPKKs) is thought to be the sole activation mechanism. Here, we report an unexpected activation mechanism for p38α MAPK that does not involve the prototypic kinase cascade. Rather it depends on interaction of p38α with TAB1 [transforming growth factor-β-activated protein kinase 1 (TAK1)-binding protein 1] leading to autophosphorylation and activation of p38α. We detected formation of a TRAF6-TAB1-p38α complex and showed stimulus-specific TAB1-dependent and TAB1-independent p38α activation. These findings suggest that alternative activation pathways contribute to the biological responses of p38α to various stimuli. ...
RAF activation and inhibition. A promising approach is to target the RAF protein, a crucial intermediary in cell signal transmission. Because of its preponderant role in tumor formation, pharmaceutical companies have invested considerable effort to identify molecules that inhibit RAF enzymatic activity. Although there has been some clinical success, it turns out that on the whole these inhibitors have the unfortunate habit of stimulating the growth of cancer cells instead of reducing it; a paradox that has puzzled an entire community of investigators and clinicians.. IRIC investigators recently discovered new elements to explain this paradox by showing how RAF activation requires three interconnected events involving RAF and RAS and how the drugs currently available unexpectedly stimulate some of those interactions. This new understanding at the molecular level results in being able to propose characteristics that the new generation of RAF inhibitors must possess to constitute effective cancer ...
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This site contains prices and technical information for products manufactured and sold by LC Laboratories. LC Laboratories manufactures laboratory reagents used to study signal transduction processes in cells and tissues in biomedical research. Signal transduction comprises the process by which communications between cells in an organism are transmitted from the outside surface of the cells into internal regions. LC Labs' products, which are the highest quality and lowest priced in the market, are produced either by: 1) isolation and/or semi-synthetic modification of natural products using preparative liquid chromatography (HPLC); or 2) multi-step total synthesis.
I have started measuring in-situ Protein Kinase C activity in permeabilized cells grown in 96-well plates, based on a few references from the literature such as: Heasley L.E., J.Biol.Chem., 1989, 264, 8646. I always get high activity after stimulation with phorbol esters and very low activity after treatment with PKC inhibitors. The problem is that the activity in untreated cells is often almost as high as in stimulated cells. Any advice or protocol would be welcome. Thanks Bernard medbpl at emory.edu ...
Proteins are the most abundant biological cellular macromolcules and structurally characterized by being formed from a group of 20 precursor molecules, known as amino acids. The grouping and combination of these amino acids enable peptides, oligopeptides and polypetides to be formed, to construct larger structures, which are strictly speaking proteins.. Although up until now it was accepted that the majority of amino acids were in the form of L-stereoisomers, it has recently been demonstrated that D-aminoacids are also present in animals and human beings in high concentrations, and they perform specific biological functions. Two D-amino acids, namely D-serine and D-aspartate, are found in considerable concentrations in the central nervous system. D-serine has shown that it is relevant to the physiological activation of the NMDA (NMDAR) receptor, and all disorders associated with a modified function of the NMDAR, such as schizophrenia, ischemia, epilepsy and neurodegenerative disorders. On the ...
Sluyter, R., Shemon, A. & Wiley, J. S. (2007). P2X7 receptor activation causes phosphatidylserine exposure in human erythrocytes. Biochemical and Biophysical Research Communications, 355 169-173 ...
The Ka value of HNO3 is about 24. HNO3 is the chemical formula for strong nitric acid. The Ka value, also known as the acid dissociation equilibrium constant, is a measure of the acidity of a...
It is a member of the 14-3-3 family which consists of 30kDa proteins that are involved in multiple protein kinase signaling pathways, regulation of…
... MAPK 経路 LIMK, subsequent phosphorylation of cofilin, and migration of major human T cells in the three dimen
Obesity is caused by damage to stem cells from aging. This damage is caused at the level of the telomeres and is reversible by telomerase activation
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Browse our collection of workplace homicides information for news stories, slideshows, opinion pieces and related videos posted on AOL.com.
Protein kinases have become central in the efforts to understand the nature of various diseases, and a lot is invested into creating effective therapeutic strategies and finding effective and selective protein kinase inhibitors. In order to succeed it is also important to focus on the structure of the kinases, their exact biological role, and how they interact and cooperate in the signaling. The exact structure of MAPKAPK5 is still unknown, and selective inhibitors are yet to be identified. Even though some of its biological roles are starting to emerge more work is required, including searching for selective inhibitors, analyzing its structure and interactions with its interaction partners. In order to analyze the structure of MAPKAPK5, homology models were generated and their ability to discriminate between binders and non-binders were analyzed. Based on the results, one model was found satisfactory and may be used as a working tool for further experimental studies and possibly structure aided ...
TY - JOUR. T1 - The Mechanism of Heat Shock Activation of ERK Mitogen-activated Protein Kinases in the Interleukin 3-dependent ProB Cell Line BaF3. AU - Ng, D.C.H.. AU - Bogoyevitch, M.A.. PY - 2000. Y1 - 2000. M3 - Article. VL - 275. SP - 40856. EP - 40866. JO - The Journal of Biological Chemistry. JF - The Journal of Biological Chemistry. SN - 0021-9258. IS - 52. ER - ...
As the colonic epithelium is physiologically exposed to butyrate and to activators of protein kinase C, we examined the effect of the protein kinase C signalling pathway on butyrate-induced expression of markers of differentiation. Activators and inhibitors of protein kinase C were used in combination with butyrate and effects on the expression of markers of differentiation examined in colon cancer cell lines. When the protein kinase C activator phorbol myristate acetate (100 nM) was added for 24 h prior to the addition of 2 mM butyrate, there was a synergistic increase in alkaline phosphatase activity (154 ± 11% above that for butyrate alone, P = 0.003) in a concentration- and time-dependent manner. Butyrate-induced expression of carcinoembryonic antigen and interleukin-8, dome formation and cell turnover were also markedly augmented by pre-treatment with phorbol myristate acetate. A similar effect was observed with propionate or acetate (but not other differentiating agents), when phorbol ...
TT-232 is a somatostatin analogue containing a five-residue ring structure. The present report describes TT-232-induced signalling events in A431 cells, where a 4-h preincubation with the peptide irreversibly induced a cell death program, which involves DNA-laddering and the appearance of shrunken nuclei, but is unrelated to somatostatin signalling. Early intracellular signals of TT-232 include a transient two-fold activation of the extracellular signal-regulated kinase (ERK2) and a strong and sustained activation of the stress-activated protein kinases c-Jun NH(2)-terminal kinase (JNK)/SAPK and p38MAPK. Blocking the signalling to ERK or p38MAPK activation had no effect on the TT-232-induced cell killing. At the commitment time for inducing cell death, TT-232 decreased EGFR-tyrosine phosphorylation and prevented epidermial growth factor (EGF)-induced events like cRaf-1 and ERK2 activation. Signalling to ERK activation by FCS, phorbol 12-myristate 13-acetate (PMA) and platelet-derived growth ...
Phosphorylation in the activation segment of protein kinases is a common mechanism of kinase regulation. However, activation loop phosphorylation of many kinases generally induces activating structural changes by repositioning key structural elements that permit substrate and cofactor binding and efficient catalysis (51). Although no common mechanism has been proposed for negative regulation of protein-Ser/Thr kinases, phosphorylation of several of the CDKs within the subdomain I GXGXXG motif at the Thr14 and Tyr15 (human CDK1 numbering) are known to be inhibitory (67-69), and acetylation of the ATP coordinating Lys has been shown to reduce the kinase activity of CDK9 (70).. Here, we establish for the first time that mimicking phosphorylation of PLK1 on Tyr217 in the P+1 loop completely inhibits detectable kinase activity, likely through inhibition of substrate binding, although we cannot formally rule out the possibility that the effect is due to the Glu substitution rather than a ...
Introduction: Cardiac overexpression of muscle specific caveolin-3 (Cav3) protects against ischemic/reperfusion injury through Akt kinase activation. However, the mechanism by which Cav3 regulates Akt activation remains unclear. We tested the hypothesis that Cav3 regulates Akt activity by directly modulating Akt activation loop phosphorylation (T308 in Akt1).. Methods and Results: Adult mouse cardiac myocytes were infected with an adeno-virus that expressed Cav3 and GFP (Ad-GFP/Cav3). In the absence of serum, Cav3 overexpression did not significantly promote T308 phosphorylation. However, when myocytes were stimulated with insulin for 15 minutes, Cav3 synergized with insulin to induce T308 phosphorylation (Ad-GFP-In: 6.9±1.3, Ad-GFP/Cav3-In: 13.7±0.8, p,0.01). The cholesterol-depleting lipid raft inhibitor, cyclodextrin (CyDex), prevented Cav3-mediated Akt activation, suggesting that Cav3 regulates Akt activation through lipid rafts. To test whether lipid rafts directly modulate Akt-T308 ...
Inhibition of MAPKs and activator protein-1. MAPKs have been implicated in many physiologic processes, including cell proliferation, differentiation, and death. There are three major types of MAPKs in mammalian cells, the extracellular signal-regulated protein kinases (ERK), the p38 MAPKs, and the c-Jun NH2-terminal kinases (JNK). The major pathways that lie downstream of the membrane-associated receptor tyrosine kinases (RTK) are shown in Fig. 1. In this cascade, Ras interacts with and activates Raf-1, which in turn phosphorylates and activates MAP/ERK kinase 1/2 (MEK1/2). Activated MEK1/2 then phosphorylates ERK1/2. The JNK1/2/3 and p38α/β/γ pathways are parallel MAPK cascades in mammalian cells. Once activated, MAPKs (ERK, JNK, and p38) activate ELK and c-Jun. Phosphoinositide 3-kinase (PI3K) is activated by RTKs and it synthesizes the second messenger, phosphatidyl inositol-3,4,5-triphosphate, which is necessary for phosphorylation of Akt. Akt directly phosphorylates the proapoptotic ...
PRAK antibody [N3C3] (mitogen-activated protein kinase-activated protein kinase 5) for ICC/IF, WB. Anti-PRAK pAb (GTX107938) is tested in Human samples. 100% Ab-Assurance.
Platelet-derived growth factor (PDGF) is a family of signaling molecules that stimulates cell growth, survival and migration. PDGF is recognized by specific transmembrane proteins, the PDGF receptors, which relay the signals to the cell activating the Mitogen-activated protein (MAP) kinases and other signaling pathways. Aberrant activation of these pathways is frequently detected in cancer. Hence, the study of these processes is essential for identifying potential drug targets or diagnostic markers.. In paper I, we identified Receptor Subfamily 4 Group A Member 1 NR4A1 to be regulated by PDGF via MAP kinases, clarifying the role of Extracellular signal-regulated kinases (Erk) 1/2, Erk5 and Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in its regulation. NR4A1 was found to be important for the tumorigenic potential, measured as anchorage-independent growth, of glioblastoma cells.. Since the cellular responses elicited by PDGF result from the balance between phosphorylation ...
Recently, we demonstrated that interaction of multimeric HIV-1 envelope gp120 with the CD4 receptor induces T cell activation, resulting both in NF-κB nuclear translocation and AP-1 activation. Furthermore, analysis of biochemical events generated upon HIV-CD4 interaction was found to activate several cellular kinases, including p56lck, Raf-1, and ERK-2, suggesting a possible involvement of a Raf-1-dependent ERK signaling pathway in this process. The purpose of this study was to investigate the role of MEK and ERK in the signal-transduction pathway(s) leading to AP-1 and NF-κB activation following engagement of CD4 with HIV-1. We demonstrate in this study that both MEK-1 and ERK-1 are dowstream cellular intermediates in this CD4 receptor-dependent activation cascade that are required for efficient activation of the two DNA-binding proteins.. Although the signaling pathway that leads to AP-1 activation following engagement of CD4 with HIV-1 was not known, it is well established that AP-1 ...
Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnRHR is coupled to Gq/11 proteins to activate phospholipase C which transmits its signal to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG activates the intracellular protein kinase C (PKC) pathway and IP3 stimulates release of intracellular calcium. In addition to the classical Gq/11, coupling of Gs is occasionally observed in a cell-specific fashion. Signaling downstream of protein kinase C (PKC) leads to transactivation of the epidermal growth factor (EGF) receptor and activation of mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. Active MAPKs translocate to the nucleus, resulting in activation of transcription factors and rapid induction of early genes ...
The MAP kinase p38 is activated by noncanonical BMP signaling, and also by cellular stress, with p38 activity providing a second readout of intrinsic and extrinsic function. If Gdf6a promotes apoptosis by increasing cell stress, upregulated p38 activity would be observed in mutants, while the converse would occur if p38 is a mediator of Gdf6a signaling. Compared with gdf6a+/+ siblings (Fig. 4A), gdf6a−/− embryos exhibit markedly increased ocular p38 MAP kinase phosphorylation assessed with whole-mount IHC using phospho-specific (Thr180/Tyr182) p38 MAP kinase antibodies (Fig. 4B). If such increased levels of phosphorylated-p38 MAP kinases activate apoptosis, inhibition of this kinase would be expected to rescue the gdf6a −/− cell death phenotype. To test this, we applied a pharmacologic inhibitor of p38 MAP kinase (SB203580 [60 μM]) to zebrafish embryos and examined apoptosis using caspase-3 IHC. Treatment with SB203580 partially inhibits the increased ocular caspase-3 activation of ...
Tyrosine kinase-mediated signaling pathways are characteristically concerned in the activation response of microglia to stimulation
Upon agonist stimulation, α1B-adrenergic receptors (α1B-ARs) couple to Gq, calcium signaling and protein kinase C activation; subsequently, the receptors are phosphorylated, desensitized and internalized. Internalization seems to involve scaffolding proteins, such as α-arrestin and clathrin. However, the fine mechanisms that participate remain unsolved. The roles of protein kinase C and the small GTPase, Rab9, in α1B-AR vesicular traffic were investigated by studying α1B-adrenergic receptor-Rab protein interactions, using Forster resonance energy transfer (FRET), confocal microscopy, and intracellular calcium quantitation. In HEK293 cells overexpressing DsRed-tagged α1B-ARs and EGFP-tagged Rab proteins, pharmacological protein kinase C activation mimicked α1B-AR traffic elicited by non-related agents, such as sphingosine 1-phosphate, i.e., transient α1B-AR-Rab5 FRET signal followed by a sustained α1B-AR-Rab9 interaction, suggesting brief receptor localization in early endosomes and ...
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First let me go back to my concerns about curcumin. Curcumin is a c-Jun NH(2)-terminal kinase (JNK) inhibitor. [1,2] This thing, a c-Jun NH(2)-terminal kinase (JNK) is also known as a stress-activated protein kinase (SAPK). Even the abbreviation SAPK is a mouthful but anyway, SAPK activation is necessary for cell death in response to exposure to certain forms of stress (including various chemotherapeutic agents) and defects in SAPK signaling promote cell survival. In other words curcumin makes it harder for stress or injury to kill a cell. Generally this is a good thing except when the stress and trauma happen to be chemotherapy which you are giving on purpose to kill cells. The study which started this entire worry showed that in a test tube, breast cancer cells being treated with Adriamycin or Cytoxan were somewhat protected by curcumin.[3 ...
Welcome to Recharge Biomedical, home of Dr. Ed Park and TA-65. Telomerase activation recharges your stem cells making you younger naturally, from the inside out
This collection of references is based on Cardioprotection induced by Na1/K1-ATPase activation involves extracellular signal-regulated kinase 1/2 and phosphoinositide 3-kinase/Akt pathway: Chronic heart failure (CHF) is a common, costly, disabling, and deadly condition in which a problem with the st ... ...
This collection of references is based on Cardioprotection induced by Na1/K1-ATPase activation involves extracellular signal-regulated kinase 1/2 and phosphoinositide 3-kinase/Akt pathway: Chronic heart failure (CHF) is a common, costly, disabling, and deadly condition in which a problem with the st ... ...
Kit Component:- KN206583G1, MAPK11 gRNA vector 1 in pCas-Guide vector- KN206583G2, MAPK11 gRNA vector 2 in pCas-Guide vector- KN206583D, donor vector…
S. Chatterjee, P. Mizar, R. Cassel, R. Neidl, B. R. Selvi, D.V Mohankrishna, B. Vedamurthy, A. Schneider, O. Bousiges, C. Mathis, J.C. Cassel, M. Eswaramoorthy, T. K. Kundu and A. L. Boutillier, A novel activator of CBP/p300 acetyltransferases promotes neurogenesis and extends memory duration in adult mice, J. Neuro Science 33, 10698 - 10712 (2013 ...
Effects of PKC activators on ACh-induced increases in [Ca2+]i. Fura-2 loaded endothelial cells were treated with ACh (3 μmol/L) followed by washing. Cells were
2. Most likely this is the result of a positive feedback mechanism, because if it was negative feedback, the production of the substance would most likely cease when it reaches high concentrations (e.g. d[A]/dt = -k [A]). A positive feedback mechanism, however, requires a brake, which, in this scenario, may not have been present, thus leading to the overproduction of the substance ...
|p| Ro 31-8220 is a selective inhibitor of protein kinase C (PKC) with IC50 values of 5, 24, 14, 27, and 24 nM for PKC α, PKC βI, PKC βII, PKC γ and PKC ε, respectively [1]. |/p| |p| PKC is a monomeric Ca2+- and phospholipid-dependent Ser/Thr protein kin
Background Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein. Also acts as a Ras responsive E3 ubiquitin ligase that, on activation...
p38 MAPK inhibitors (inhibiting targets of signaling pathways) used for various assays, some have entered clinical trials, which would be new cancer therapies.
ERK3/4. ERK3 (MAPK6) and ERK4 (MAPK4) are structurally related atypical MAPKs possessing SEG motifs in the activation loop and displaying major differences only in the C-terminal extension. ERK3 and ERK4 are primarily cytoplasmic proteins which bind, translocate and activate MK5 (PRAK, MAPKAP5). ERK3 is unstable, unlike ERK4 which is relatively stable.[12] ...
The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. Cell culture and animal studies have demonstrated that MK5 is involved in tumour suppression and promotion, embryogenesis, anxiety, cell motility and cell cycle regulation. In the present study, homology models of MK5 were used for molecular dynamics (MD) simulations of: (1) MK5 alone; (2) MK5 in complex with an inhibitor; and (3) MK5 in complex with the interaction partner p38α. The calculations showed that the inhibitor occupied the active site and disrupted the intramolecular network of amino acids. However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that not only the p38 docking region, but also amino acids in the activation segment, αH helix, P-loop, regulatory phosphorylation region and the C-terminal of MK5 may be involved in forming a very stable MK5-p38α complex, and that p38α
TY - JOUR. T1 - Biochemical basis for the functional switch that regulates hepatocyte growth factor receptor tyrosine kinase activation. AU - Sheth, Payal R.. AU - Hays, John L.. AU - Elferink, Lisa. AU - Watowich, Stanley. PY - 2008/4/1. Y1 - 2008/4/1. N2 - Ligand-induced dimerization of receptor tyrosine kinases (RTKs) modulates a system of linked biochemical reactions, sharply switching the RTK from a quiescent state to an active state that becomes phosphorylated and triggers intracellular signaling pathways. To improve our understanding of this molecular switch, we developed a quantitative model for hepatocyte growth factor receptor (c-MET) activation using parameters derived in large part from c-MET kinetic and thermodynamic experiments. Our model accurately produces the qualitative and quantitative dynamic features of c-MET phosphorylation observed in cells following ligand binding, including a rapid transient buildup of phosphorylated c-MET at high ligand concentrations. In addition, our ...
The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway. ...
Complement factor C3, recently found to contain covalently bound phosphate, was phosphorylated in vitro by cyclic AMP-dependent protein kinase (protein kinase A) and Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C). Both protein kinases phosphorylated the same serine residue(s) located in the C3a portion of the alpha-chain. In addition, protein kinase C phosphorylated the beta-chain to a lesser extent. Protein kinase A gave a maximal incorporation of 1 mol of phosphate/mol of C3 while that value with protein kinase C was 1.5 mol of phosphate/mol of C3. The velocity in pmol of [32P]phosphate/(min x unit kinase) was 20 times higher for protein kinase C than for protein kinase A although a 10 times lower ratio of protein kinase to C3 was used in the former case. The apparent Kmfor C3 was 2.6 µM when protein kinase C was used. The phosphorylated C3 was found to be more resistant to partial degradation by trypsin than unphosphorylated C3. It was also found that ...
MAPK8 [ENSP00000378974]. Stress-activated protein kinase JNK1; Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including ...
Background: Alzheimers Disease (AD) is a neuron related brain disorder leading to reasoning and memory loss. There is no specific cure identified for AD. JNK3 (c-Jun N-terminal kinase /stress-activated protein kinase) are highly revealed within the central nervous system, particularly neurons, playing vital role in functioning of brain. JNK3 hyper phosphorylation is a very common conclusion in neurodegenerative diseases. JNK3 in turn hyper phosphorylates Amyloid Precursor Protein (APP) which leads to the formation of Amyloid β peptides (an inductive agent of Alzheimers disease). Methods: Protein JNK-3 (PDB ID: 3KVX) was retrieved from protein data bank and later we docked a library of compounds against it. These were further validated by ADMET studies. Results: Thus, docking inhibitors of JNK3 may provide a promising sanitive approach. Based on best docking score and glide score a potential lead is identified against JNK3. Conclusion: Inhibiting JNK-3 may lead to less production of amyloidβ ...
Sun QY.,Wu GM.,Lai LX.,Bonk A.,Cabot R.,...&Schatten H.(2002).Regulation of mitogen-activated protein kinase phosphorylation, microtubule organization, chromatin behavior, and cell cycle progression by protein phosphatases during pig oocyte maturation and fertilization in vitro.Biology of Reproduction,66(3),580-588 ...
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Delayed cytoprotection (preconditioning) occurs 24h after sublethal simulated ischaemia and reperfusion (SI/R) in neonatal rat ventricular cardiomyocytes. SI/R was used to investigate the role of activation of mitogen-activated protein kinases (MAPKs), stress-activated protein kinases (SAPKs) and phosphoinositide 3-kinase-dependent protein kinase B (PKB)/Akt in cytoprotection. SI resulted in transient dual (Thr/Tyr) phosphorylation of p42/p44-MAPK and p38-MAPK, weak phosphorylation of p46/p54-SAPK, but no phosphorylation of PKB. Reperfusion caused further transient phosphorylation of p38-MAPK, but sustained phosphorylation of p42/p44-MAPK (lasting 4h) and of Ser473 of PKB (lasting 2h). Furthermore, SI/R (24h) induced delayed protection against lethal SI, as determined by an increase in cell viability {bioreduction of MTT [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide]} and a decrease in cell injury (release of creatine kinase). Both protection and phosphorylation of ...
TY - JOUR. T1 - Multiple forms of brain adenylate cyclase. T2 - Stimulation by Mn2+. AU - Malamuda, Daniel F.. AU - DiRusso, Concetta C.. AU - Aprille, June R.. PY - 1977/11/23. Y1 - 1977/11/23. N2 - Mn2+-stimulated adenylate cyclase (ATP pyrophosphate-lyase-(cyclizing), EC 4.6.1.1) activity in detergent solubilized preparations from mouse brain. While NaF-stimulated activity was decreased by both solubilization and storage at 0-4°C, the ability of the enzyme to be stimulated by Mn2+ was maintained for up to one week. By including Mn+ in the assay of adenylate cyclase in gel fractions after isoelectric focusing, two distinct peaks of enzyme activity (pI1 = 5.8, pI2 = 6.4) were detected, suggesting the existence of more than one type of catalytic subunit in mouse brain cell membranes.. AB - Mn2+-stimulated adenylate cyclase (ATP pyrophosphate-lyase-(cyclizing), EC 4.6.1.1) activity in detergent solubilized preparations from mouse brain. While NaF-stimulated activity was decreased by both ...
MK08_HUMAN] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In ...
A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. The stable beta-globin mRNA was rendered unstable by insertion of the 2, 500-nucleotide Cox-2 3 untranslated region (3 UTR). The chimeric transcript was stabilized by a constitutively active form of MAPK kinase 6, an activator of p38. This stabilization was blocked by SB203580, an inhibitor of p38, and by two different dominant negative forms of MAPK-activated protein kinase 2 (MAPKAPK-2), a kinase lying downstream of p38. Constitutively active MAPKAPK-2 was also able to stabilize chimeric beta-globin-Cox-2 transcripts. The MAPKAPK-2 substrate hsp27 may be involved in stabilization, as beta-globin-Cox-2 transcripts were partially stabilized by phosphomimetic mutant forms of hsp27. A short (123-nucleotide) fragment of the Cox-2 3 UTR was necessary and sufficient for the regulation of mRNA stability by the p38
Nitric oxide (NO) is a gaseous compound that serves as a signaling molecule in cellular interactions. In the vasculature, NO is synthesized from endogenous agents by endothelial nitric oxide synthase (eNOS) where it plays key roles in several functions related to homeostasis, adaptation, and development. Recent experimental studies have revealed cycles of increasing and decreasing NO production when eNOS is stimulated by factors such as glucose or insulin. We offer a mathematical model of a generic amino acid receptor site on eNOS wherein this species is subject to activation/deactivation by a pair of interactive kinase and phosphatase species. The enzyme kinetic model is presented as a system of ordinary differential equations including time delay to allow for various intermediate, unspecified complexes. We show that under conditions on the model parameters, varying the delay time may give rise to a Hopf bifurcation. Properties of the bifurcating solutions are explored via a center manifold reduction,
The cell signaling docking protein p130cas became tyrosine-phosphorylated in SH-SY5Y human neuroblastoma cells during induced differentiation with 12-O-tetradecanoylphorbol-13-acetate (TPA) and serum or a combination of basic fibroblast growth factor (bFGF) and insulin-like growth factor-I (IGF-I). The differentiating cells develop a neuronal phenotype with neurites and growth cones and sustained activation of protein kinase C (PKC) and pp60c-src. The TPA-induced p130cas phosphorylation increased within 5 min of stimulation and persisted for at least 4 days, whereas bFGF/IGF-I-induced p130cas phosphorylation was biphasic. However, the increase in tyrosine phosphorylation of p130cas was not restricted to differentiation inducing stimuli. The phosphorylation was blocked by the specific PKC inhibitor GF 109203X, and transient transfection with active PKC-epsilon induced p130cas tyrosine phosphorylation. pp60c-src, known to directly phosphorylate p130cas in other cell systems, was not activated ...