Cytokines may contribute to beta-cell apoptosis in the early stages of type 1 diabetes mellitus. It has been reported recently that interleukin-1 beta (IL-1 beta) induces activation of the mitogen-activated protein kinases (MAPK) p38 and ERK1/2 in neonatal rat islets. Since these kinases may partici …
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 ...
Figure 4: Effects of 50 μM DHA, EPA, SA, and PA or 25 μM OA and LA on IL-2-induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Lymphocytes were incubated with 5 μg/mL ConA for 24 h. Afterwards, lymphocytes were washed with PBS and cultured with the different fatty acids in the presence or absence of IL-2 (30 ng/mL) for 1 h. Total proteins were extracted from lymphocytes for western-blotting analysis. Blots were analyzed by densitometry and the results normalized to their respective controls, which were set to a value of 100% for each experiment. The values are presented as the means ± SEM. ###p,0.001 for comparison with the control in the absence IL-2); *p,0.05, **p,0.01, and ***p,0.001 for comparison with the control treated with IL-2 ...
The Alpha SureFire® Ultra™ HV Multiplex p-ERK 1/2 + Total ERK assay kit is used to measure both the phosphorylation (Thr202/Tyr204) and total levels of endogenous
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 ...
Ovarian cancer is a complex disease with heterogeneity among the gene expression molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal (Mes) subtype have a poorer prognosis than patients with tumors of an epithelial (Epi) subtype. We evaluated GEMS of ovarian cancer patients for molecular signaling profiles and assessed how the differences in these profiles could be leveraged to improve patient clinical outcome. Kinome enrichment analysis identified AXL as a particularly abundant kinase in Mes-subtype tumor tissue and cell lines. In Mes cells, upon activation by its ligand GAS6, AXL coclustered with and transactivated the receptor tyrosine kinases (RTKs) cMET, EGFR, and HER2, producing sustained extracellular signal-regulated kinase (ERK) activation. In Epi-A cells, AXL was less abundant and induced a transient activation of ERK without evidence of RTK transactivation. AXL-RTK crosstalk also stimulated sustained activation of the transcription factor FRA1, which ...
Although transforming growth factor β (TGF-β) is known to be a potent growth inhibitor of breast cancer cells (BCCs), the signaling mechanisms mediating TGF-β responses have not been defined. We have demonstrated previously that TGF-β can activate Ras and extracellular signal-regulated kinase (ERK) 1 in untransformed epithelial cells (K. M. Mulder and S. L. Morris, J. Biol. Chem., 267: 5029-5031, 1992; M. T. Hartsough and K. M. Mulder, J. Biol. Chem., 270: 7117-7124, 1995). We have also shown that TGF-β signaling is altered in epithelial cells when Ras activation is blocked (Hartsough et al., J. Biol. Chem., 271: 22368-22375). Here we demonstrate the ability of the TGF-β3 isoform to activate the signaling component ERK2 in TGF-β-sensitive BCCs but not in TGF-β-resistant cells. The ERK2 isoform was activated by 6-fold within 10 min of TGF-β3 addition to the TGF-β-sensitive BCC line Hs578T. Moreover, the IC50 for inhibition of DNA synthesis by TGF-β3 in this cell line correlated with ...
Gooney M, Shaw K, Kelly Á, OMara SM, Lynch MA. Gooney M, Shaw K, Kelly A, OMara SM, Lynch MA. Gooney M, Shaw K, Kelly A, OMara SM, Lynch MA., Long-term potentiation and spatial learning are associated with increased phosphorylation of TrkB and extracellular signal-regulated kinase (ERK) in the dentate gyrus: evidence for a role for brain-derived neurotrophic factor., Behavioural Neuroscience, 116, (3), 2002, p455 - 463 Journal Article, 2002 URL ...
To determine how extracellular signal-regulated kinases (ERK) 1/2 promote mammary tumorigenesis, we examined the real-time behavior of cells in an organotypic culture of the mammary glandular epithelium. Inducible activation of ERK1/2 in mature acini elicits cell motility and disrupts epithelial arc …
The extracellular-signal-regulated kinase (ERK) pathway is one of the major signaling cassettes of the mitogen activated protein kinase (MAPK) signaling ..
The mammalian genome contains two mitogen-activated protein kinase (MAPK) kinase (MEK)-encoding genes, Mek1 and Mek2. MEKs phosphorylate and activate the two extracellular signal-regulated kinase (ERK) isoforms ERK1 and ERK2. Mek1−/− embryos die due to placental defects, whereas Mek2−/− mice survive with a normal life span and fertility, suggesting that MEK1 has functions not shared by MEK2. However, most Mek1+/−Mek2+/− embryos also die from placental defects, indicating that both Mek genes contribute to placental development. To assess the functional specificity of the Mek1 and Mek2 genes, we produced a Mek1 knock-in allele in which the Mek2 coding sequences were placed under the control of Mek1 regulatory sequences (Mek12 allele). Mek12/2 mice were viable with no apparent phenotype, indicating rescue by MEK2 and functional redundancy between the two MEK proteins. However, Mek12/− embryos with Mek2 in only one of the Mek1 alleles and the other Mek1 allele null died from abnormal ...
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008 ...
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 ...
The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described.[3] ...
Ran-Binding Protein M (RanBPM) has been previously shown to inhibit c-Raf expression, however how this was achieved remains unclear. c-Raf is the central component of the extracellular signal-regulated kinase (ERK) pathway which has been linked to many cancer types. Furthermore, RanBPM was recently identified as part of the E3 ubiquitin ligase complex and the CTLH (C-terminal to LisH) complex (McTavish et al., 2019). Lastly, RanBPM has been linked to various signaling pathways related to numerous cellular processes which include - apoptosis, cell adhesion, migration, transcription, nuclear-cytoplasmic transport and also plays a significant role during development (Salemi et al., 2017). ...
TY - JOUR. T1 - Intestinal trefoil factor (TFF-3) and extracellular signal-regulated kinase (ERK) in cholangiocarcinoma. AU - Ailawadhi, Sikander. AU - Nagase, Hiroki. AU - Khoury, Thaer. AU - Yu, Jihnhee. AU - Tan, Dongfeng. AU - Black, Jennifer. AU - Brattain, Michael. AU - Javle, Milind. PY - 2007/7. Y1 - 2007/7. N2 - Background/Aims: The mucin-associated trefoil factor (TFF) peptides are integral to cytoprotection. TFF-3 is aberrantly expressed in colorectal and hepatocellular cancer and associated with an invasive phenotype. TFF-3 is also expressed in normal biliary epithelium. However, its role in biliary cancers is unknown. The biological effects of TFFs may result from EGFR, PI3 kinase, COX-2 and STAT-mediated signaling. We investigated the expression of TFF-3, Erk, Akt, EGFR and COX-2 in biliary cancer. Methodology: Twenty-four consecutive cases of cholangiocarcinoma treated from 1996-2002 were studied. Immunohistochemistry was performed using monoclonal antibodies to TFF-3, EGFR, ...
Mutational activation of Ras (H-Ras, K-Ras, and N-Ras) is associated with a diverse spectrum of human cancers (1). For example, 50% of colorectal carcinomas harbor mutated K-RAS, and 25% of melanomas contain mutated N-RAS alleles. Consequently, there is considerable interest and effort in the development of anti-Ras strategies for cancer treatment (2, 3). One approach involves the inhibition of Ras-mediated signal transduction. Of these efforts, inhibitors of signaling mediated by the Ras effectors, the Raf serine/threonine kinases (c-Raf-1, A-Raf, and B-Raf), have attracted the most interest. Ras promotes Raf activation, which in turn, activates the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) 1 and MEK2 dual-specificity protein kinases. MEK1/2 kinases then activate the ERK1 and ERK2 mitogen-activated protein kinases and inhibitors of this cascade have been developed and are currently under evaluation in clinical trials (4). These include kinase ...
We aimed to investigate specific roles of mitogen-activated protein kinases (MAPK) in the deterioration of endothelial function during the progression of diabetes and the potential therapeutic effects of MAPK inhibitors and agonists in the amelioration of endothelial function. Protein expression and phosphorylation of p38, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (Erk) were assessed in mesenteric arteries of 3- (3M) and 9-month-old (9M) male diabetic and control mice. The expression of p38, JNK, and Erk was comparable in all groups of mice, but the phosphorylation of p38 and JNK was increased in 3M and further increased in 9M diabetic mice, whereas the phosphorylation of Erk was substantially reduced in 9M diabetic mice. NADPH oxidase-dependent superoxide production was significantly increased in vessels of two ages of diabetic mice. Inhibition of either p38 with SB203580 or JNK with SP600125 reduced superoxide production and improved shear stress-induced ...
Gene Information This gene encodes an evolutionarily conserved protein associated with cell apoptosis. The protein interacts with the serine/threonine protein kinase MST4 to modulate the extracellular signal-regulated kinase (ERK) pathway. It also interacts with and is phosphoryated by serine/threonine kinase 25 and is thought to function in a signaling pathway essential for vascular developent. Mutations in this gene are one cause of cerebral cavernous malformations which are vascular malformations that cause seizures and cerebral hemorrhages. Multiple alternatively spliced variants encoding the same protein have been identified. [provided by RefSeq Jul 2008]. ...
History and purpose: Trabecular meshwork (TM) can be an ocular cells mixed up in rules of aqueous humour outflow and intraocular pressure (IOP). and mobilization of intracellular Ca2+ shops. A PTX-sensitive upsurge in extracellular signal-regulated kinase (ERK1/2) phosphorylation was also seen in response to WIN55 212 indicative of the Gi/o signalling pathway. CB1-Gq/11 coupling to activate PLC-dependent raises in Ca2+ were particular to WIN55 212 and werent observed with additional.. Read More. ...
Huntingtons disease (HD) is an inherited, progressive and ultimately fatal neurodegenerative disorder that is characterized by psychiatric, cognitive and motor symptoms. Among the pathways implicated in HD are those involving mitogen-activated protein kinase signaling and particularly the Ras-extracellular signal-regulated kinase (ERK) cascade. Studies in both cells and animal models suggest that ERK activation might provide a novel therapeutic target for the treatment of HD but compounds that specifically activate ERK are few. To test the hypothesis that pharmaceutical activation of ERK might be protective for HD, a polyphenol, fisetin, which was previously shown to activate the Ras-ERK cascade, was tested in three different models of HD: PC12 cells expressing mutant Httex1 under the control of an inducible promoter, Drosophila expressing mutant Httex1 and the R6/2 mouse model of HD. The results indicate that fisetin can reduce the impact of mutant huntingtin in each of these disease models. ...
|p|SL-327 is a selective inhibitor of MEK1 and MEK2 with IC50 values of 0.18 and 0.22μM,  respectively.|br /|MEK1 and MEK2 (ERK) are a kinase enzyme which phosphorylate mitogen-activated protein kinase (MAPK). Extracellular signal-regulated kinase
Fujishita Teruaki , Kajino-Sakamoto Rie , Kojima Yasushi , Taketo Makoto Mark , Aoki Masahiro Extracellular signal-regulated kinase is an MAPK that is most closely associated with cell proliferation, and the MEK/ERK signaling pathway is implicated in various human cancers. Although epidermal g … Cancer Science 106(6), 692-699, 2015-06 IR Ichushi Web ...
ERK1 / ERK2, 0.1 ml. Erk1 and Erk2 are closely related mitogen activated protein (MAP) kinases which are activated by many growth factors, mitogens and differentiation-promoting agents via a protein kinase cascade.
Mitogen-activated protein kinase (MAPK)-triggered protein kinase 2 (MAPKAPK2) mediates multiple p38 MAPK-dependent inflammatory responses. at Ser-58. Computational modeling and calculation of theoretical binding energies predicted that both phosphorylation at Ser-58 and mutation of Ser-58 to Asp (S58D) jeopardized the ability of 14-3-3 to dimerize. Experimentally, S58D mutation significantly impaired both 14-3-3 dimerization and binding to Raf-1. These data suggest that MAPKAPK2-mediated phosphorylation regulates 14-3-3 functions, and this MAPKAPK2 activity may symbolize a novel pathway mediating p38 MAPK-dependent swelling. A diverse group of cellular responses are elicited by activation of a highly conserved family of mitogen-activated protein kinase (MAPK) signaling pathways, which includes extracellular signal-regulated kinases (ERKs), c-jun N-terminal kinases (JNKs), ERK5, and p38 MAPKs. A large body of evidence shows that p38 MAPK activity is critical to immune and inflammatory responses. ...
AIMS/HYPOTHESIS: The beta cell destruction and insulin deficiency that characterises type 1 diabetes mellitus is partially mediated by cytokines, such as IL-1beta, and by nitric oxide (NO)-dependent and -independent effector mechanisms. IL-1beta activates mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK), and the nuclear factor kappa B (NFkappaB) pathway. Both pathways are required for expression of the gene encoding inducible nitric oxide synthase (iNOS) and for IL-1beta-mediated beta cell death. The molecular mechanisms by which these two pathways regulate beta cell Nos2 expression are currently unknown. Therefore, the aim of this study was to clarify the putative crosstalk between MAPK and NFkappaB activation in beta cells. MATERIALS AND METHODS: The MAPKs ERK, p38 and JNK were inhibited by SB203580, PD98059 or Tat-JNK binding domain or by cells overexpressing the JNK binding domain. The effects
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 ...
Mitogen-activated protein kinases (MAPKs) are proline-directed serine and threonine protein kinases that regulate numerous physiological cell responses including: embryogenesis, cell differentiation, proliferation, migration, apoptosis and death. Extracellular signal-regulated kinases (ERKs) 1 and 2 (ERK1/2), also known as p44 MAPK and p42 MAPK respectively, belong to one of the five major groups of MAPKs. Closely-related ERK1/2 isoforms are uniquely activated by several extracellular signals including growth factors, cytokines, hormones, and neuro-transmitters. Activation of ERK1/2 by the upstream kinases MEK1 and MEK2 occurs via dual phosphorylation on specific threonine (Thr202) and tyrosine (Tyr204) residues on the T*EY* motif. MEK1 and MEK2 are activated through receptors (tyrosine kinases or integrins) via pathways involving adaptor proteins, guanine nucleotide exchange factors, small GTP binding proteins, and MAPKKs. Activated ERK1/2 phosphorylates both, cytosolic (SOS, MNK1/2, RSKs) and ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
Colorectal cancers (CRCs) that are sensitive to the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab or panitumumab almost always develop resistance within several months of initiating therapy. We report the emergence of polyclonal KRAS, NRAS, and BRAF mutations in CRC cells with acquired resistance to EGFR blockade. Regardless of the genetic alterations, resistant cells consistently displayed mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) activation, which persisted after EGFR blockade. Inhibition of MEK1/2 alone failed to impair the growth of resistant cells in vitro and in vivo. An RNA interference screen demonstrated that suppression of EGFR, together with silencing of MEK1/2, was required to hamper the proliferation of resistant cells. Indeed, concomitant pharmacological blockade of MEK and EGFR induced prolonged ERK inhibition and severely impaired the growth of resistant tumor cells. Heterogeneous and concomitant mutations in ...
Extracellular signal-regulated kinase (ERK) activation has been implicated in cell motility and invasion. In this study, we demonstrated that the steady-state levels of activated ERK1/2 correlated with the degree of invasiveness and metastatic potential of three Dunning cancer cell lines, originating from the same parental tumor. Inhibition of mitogen-activated protein kinase kinase 1 (MEK1), an upstream regulator of ERK1/2, with PD98059 resulted in a dose-dependent reduction of invasiveness with different IC 50 values in the three Dunning cell lines. These results suggest that ERK is, at least in part, responsible for regulating invasiveness and may underlie the differences in the metastatic ability of the cell lines ...
MAPKK 6 is a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress-induced cell cycle arrest, transcription activation and apoptosis.[6] ...
Mammalian MAPK pathways are difficult to assign because of the many kinases, cell lines, tissue types, experimental conditions (which can yield conflicting results) and functional redundancy. Genetic analysis in Drosophila melanogaster and Caenorhabditis elegans has greatly helped, however (Chang and Karin, 2001). Five families of MAPKs have been defined in mammalian cells: extracellular signal-regulated kinases (ERK1 and ERK2), Jun N-terminal kinases (JNK1, JNK2 and JNK3); p38 kinase isozymes (p38α, p38β, p38γ and p38δ); ERK3/ERK4; and ERK5 (Davis, 2000; Chen et al., 2001; Chang and Karin, 2001; Johnson and Lapadat, 2002; Roux and Blenis, 2004). The first three, and their activators, are implicated in human diseases and are targets for drug development (Manning and Davis, 2003; English and Cobb, 2002). Mammalian MAPK modules associate with numerous scaffold proteins that regulate their activity and localization in various cells (Morrison and Davis, 2003). The scaffold proteins can bind to ...
TY - JOUR. T1 - Changes in corneal basal epithelial phenotypes in an altered basement membrane. AU - Wang, I. Jong. AU - Tsai, Jui-Fang. AU - Yeh, Lung Kun. AU - Tsai, Ryan Yao Nien. AU - Hu, Fung Rong. AU - Kao, Winston W Y. PY - 2011. Y1 - 2011. N2 - Background: To examine the corneal epithelial phenotype in an altered basement membrane. Methodology/Principal Findings: Corneas from 9 patients with symptoms of continuous unstable corneal curvature (CUCC) were harvested by penetrating keratoplasty and subjected to histology examination and immunohistochemical staining with transactivating and N-terminally truncated pP63 transcript (DNp63), cytokeratin 3 (Krt3), ATP-binding cassette subfamily G member 2 (ABCG2), connexin 43 (CX43), p38 mitogen-activated protein kinases (p38MAPK), activating protein 2 (TFAP2), and extracellular signal-regulated kinase (Erk1/2) monoclonal antibodies. Positive immunostaining with ABCG2, p38MAPK, and TFAP2 monoclonal antibodies was observed in the basal epithelial ...
Purpose: Abnormal signaling through receptor tyrosine kinase (RTK) moieties is important in tumorigenesis and drug targeting of colorectal cancers. Wild-type KIT (WT-KIT), a RTK that is activated upon binding with stem cell factor (SCF), is highly expressed in some colon cancers; however, little is known about the functional role of SCF-dependent KIT activation in colon cancer pathogenesis. We aimed to elucidate the conditions and roles of WT-KIT activation in colon cancer tumorigenesis.Experimental Design: Colorectal cancers with KIT expression were characterized by immunoblotting and immunohistochemistry. The biologic alterations after KIT-SCF binding were analyzed with or without protein kinase C (PKC) activation.Results: We found that WT-KIT was expressed in a subset of colon cancer cell lines and was activated by SCF, leading to activation of downstream AKT and extracellular signal-regulated kinase (ERK) signaling pathways. We also showed that KIT expression gradually decreased, after ...
Background MEK1/2 is a serine/threonine protein that phosphorylates extracellular signal-regulated kinase (ERK1/2). Cerebral ischemia results in enhanced expression of cerebrovascular contractile...
TY - JOUR. T1 - Cell proliferation is insufficient, but loss of tuberin is necessary, for chemically induced nephrocarcinogenicity. AU - Yoon, Hae Seong. AU - Monks, Terrence J.. AU - Everitt, Jeffrey I.. AU - Walker, Cheryl L.. AU - Lau, Serrine S.. N1 - Copyright: Copyright 2020 Elsevier B.V., All rights reserved.. PY - 2002. Y1 - 2002. N2 - Although 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ; 2.5 μmol/kg ip) markedly increased cell proliferation within the outer stripe of the outer medulla (OSOM) of the kidney in both wild-type (Tsc2+/+) and mutant Eker rats (Tsc2EK/+), only TGHQ-treated Tsc2EK/+ rats developed renal tumors, indicating that cell proliferation per se was not sufficient for tumor development. Tuberin expression was initially induced within the OSOM after TGHQ treatment but was lost within TGHQ-induced renal tumors. High extracellular signal-regulated kinase (ERK) activity occurred in the OSOM of Tsc2EK/+ rats at 4 mo and in TGHQ-induced renal tumors. Cyclin D1 was also ...
The Cover. Phospholipids and lipid second messengers are important mediators of mitogenic signal transduction, but their involvement in oncogenesis and their potential as anticancer drug targets are scarcely studied. A role for phospholipases in the previously described antisignaling properties of the antitumor agent, SC-ααδ9, was investigated based on a hypothesis developed from molecular modeling studies, which suggested significant structural similarity between SC-ααδ9 (shown in yellow) and the model phospholipid, phosphatidic acid (shown in atom-specific colors). In support of this hypothesis, SC-ααδ9 was found to selectively inhibit phospholipase C (PLC) but not phospholipase D (PLD), and to cause a reduction in the activation of extracellular signal-regulated kinase (Erk) by oncogenic Ras. Modifications in one of the hydrophobic side chains were sufficient to abolish PLC inhibitory activity. For details, see 885 in this issue.. ...
Fingerprint Dive into the research topics of Activin A stimulates mitogenesis in Swiss 3T3 fibroblasts without activation of mitogen-activated protein kinases. Together they form a unique fingerprint. ...
Recombinant Mitogen-Activated Protein Kinase 8 (MAPK8) Protéine. Origine: Humain. Source: Baculovirus infected Insect Cells. Commandez ABIN593493.
Recombinant Mitogen-Activated Protein Kinase 8 (MAPK8) Protein (GST tag). Spezies: Human. Quelle: Wheat germ. Jetzt Produkt ABIN1310303 bestellen.
The discovery of resolvins has been a main breakthrough for understanding the processes involved in resolution of inflammation. and protectins [52]. The second step during resolvin synthesis is the transformation of DHA to 17systems depending on the cell type and tissue. RvE2 also enhanced phagocytosis and interleukin (IL)-10 production, suggesting that these RvE2 actions may be transduced by additional receptors that have yet to be discovered. Physique 1 Resolvin signaling pathways in different cell types. (A) In polymorphonuclear neutrophils (PMNs), RvE1 binds to ChemR23, activates Gi/o, which activates extracellular signal-regulated kinase (ERK), and eventually blocks TNF- signaling. … The RvD family shares comparable signaling mechanisms as the RvE family, as LRP2 they also activate GPCRs. Specifically, RvD1 activity is usually mediated by two GPCRs termed ALX/FPR2 and GPR32 [81,91]. The ALX/FPR2 has been shown to bind lipid and protein ligands, eliciting either anti-inflammatory or ...
Protein target information for Mitogen-activated protein kinase (pig). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
ERK1 and ERK2 (also known as MAPK3 and MAPK1) are 44 and 42 kDa Ser/Thr kinases, respectively. They are part of the Ras-Raf-ERK signal transduction cascade often found downstream of growth factor receptor activation. ERK1 and ERK2 were initially isolated and cloned as kinases activated in response to insulin and NGF. They are expressed in most, if not all, mammalian tissues. Dual threonine and tyrosine phosphorylation activate both ERKs, at Thr202/Tyr204 for human ERK1 and Thr185/Tyr187 for human ERK2 ...
Opens the Highlight Feature Bar and highlights feature annotations from the FEATURES table of the record. The Highlight Feature Bar can be used to navigate to and highlight other features and provides links to display the highlighted region separately. Links in the FEATURES table will also highlight the corresponding region of the sequence. More... ...
KO validated. Cited in 1 publication. View Human/Mouse Phospho-ERK1 (ERK1 T202/Y204, ERK2 T185/Y187) Antibody (MAB18251) validated in Human and Mouse.
stripping too much? - posted in SDS-PAGE and Western Blotting: Hi, I am doing some western blots, but seem to be having a little problem with getting my loading controls working. I have been looking at Phospho-ERK and phospho-p38, I am getting clear bands when I stain (albeit not much variation between the different samples, but thats a different problem) I am attempting to then strip my membrane to look at Total ERK or p38, or beta-actin, but then dont appear to get any bands. I am us...
TY - JOUR. T1 - Activation of mitogen-activated protein kinases by lysophosphatidylcholine- induced mitochondrial reactive oxygen species generation in endothelial cells. AU - Watanabe, Nobuo. AU - Zmijewski, Jaroslaw W.. AU - Takabe, Wakako. AU - Umezu-Goto, Makiko. AU - Le Goffe, Claire. AU - Sekine, Azusa. AU - Landar, Aimee. AU - Watanabe, Akira. AU - Aoki, Junken. AU - Arai, Hiroyuki. AU - Kodama, Tatsuhiko. AU - Murphy, Michael P.. AU - Kalyanaraman, Raman. AU - Darley-Usmar, Victor M.. AU - Noguchi, Noriko. PY - 2006/5. Y1 - 2006/5. N2 - Lysophosphatidylcholine (lysoPC) evokes diverse biological responses in vascular cells including Ca2+ mobilization, production of reactive oxygen species, and activation of the mitogen-activated protein kinases, but the mechanisms linking these events remain unclear. Here, we provide evidence that the response of mitochondria to the lysoPC-dependent increase in cytosolic Ca2+ leads to activation of the extracellular signal-regulated kinase (ERK) ...
PubMed journal article: Activation of extracellular signal-regulated protein kinase in sensory neurons after noxious gastric distention and its involvement in acute visceral pain in rats. Download Prime PubMed App to iPhone, iPad, or Android
Interferon alpha (IFN-α) is the key component of the therapy for hepatitis C virus (HCV) infection. IFN-α exerts anti-HCV activity by targeting certain signaling pathways. Using infectious HCV culture system in human hepatoma Huh7.5.1 cells, we analyzed functional relevance of extracellular signal-regulated kinase (ERK) pathway for IFN-α-mediated anti-HCV activity. IFN-α treatment resulted in activation of ERK pathway by increasing phosphorylation of c-Raf, MEK, and ERK1/2 in Huh7.5.1 cells, whereas HCV impaired such activation. IFN-α-dependent ERK1/2 phosphorylation was blocked by MEK inhibitor U0126. Pharmacological inhibition of ERK1/2 by U0126 or siRNA-mediated knockdown of ERK1/2 resulted in suppressive effects on HCV RNA levels and expression of HCV nonstructural protein 3 and envelope protein 2, establishing an important role for ERK pathway in HCV replication. Moreover, induction of a set of antiviral genes by IFN-α was enhanced in HCV-infected Huh7.5.1 cells due to the ERK1/2 knockdown,
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 ...
Late cerebral ischemia carries high morbidity and mortality after subarachnoid hemorrhage (SAH) due to reduced cerebral blood flow (CBF) and the subsequent cerebral ischemia which is associated with upregulation of contractile receptors in the vascular smooth muscle cells (SMC) via activation of mitogen-activated protein kinase (MAPK) of the extracellular signal-regulated kinase (ERK)1/2 signal pathway. We hypothesize that SAH initiates cerebrovascular ERK1/2 activation, resulting in receptor upregulation. The raf inhibitor will inhibit the molecular events upstream ERK1/2 and may provide a therapeutic window for treatment of cerebral ischemia after SAH. Here we demonstrate that SAH increases the phosphorylation level of ERK1/2 in cerebral vessels and reduces the neurology score in rats in additional with the CBF measured by an autoradiographic method. The intracisternal administration of SB-386023-b, a specific inhibitor of raf, given 6 h after SAH, aborts the receptor changes and protects the brain
Octadecaneuropeptide (ODN) and its precursor diazepam-binding inhibitor (DBI) are peptides belonging to the family of endozepines. Endozepines are exclusively produced by astroglial cells in the central nervous system of mammals, and their release is regulated by stress signals and neuroactive compounds. There is now compelling evidence that the gliopeptide ODN protects cultured neurons and astrocytes from apoptotic cell death induced by various neurotoxic agents. In vivo, ODN causes a very strong neuroprotective action against neuronal degeneration in a mouse model of Parkinsons disease. The neuroprotective activity of ODN is based on its capacity to reduce inflammation, apoptosis, and oxidative stress. The protective effects of ODN are mediated through its metabotropic receptor. This receptor activates a transduction cascade of second messengers to stimulate protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK)
C2C12 myotubes exposed to VLDL showed increased levels of ER stress and inflammatory markers whereas peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and AMP-activated protein kinase (AMPK) levels were reduced and the insulin signalling pathway was attenuated. The effects of VLDL were also observed in isolated skeletal muscle incubated with VLDL. The changes caused by VLDL were dependent on extracellular signal-regulated kinase (ERK) 1/2 since they were prevented by the ERK1/2 inhibitor U0126 or by knockdown of this kinase by siRNA transfection. ApoCIII mimicked the effects of VLDL and its effects were also blocked by ERK1/2 inhibition, suggesting that this apolipoprotein was responsible for the effects of VLDL. Skeletal muscle from transgenic mice overexpressing apoCIII showed increased levels of some ER stress and inflammatory markers and increased phosphorylated ERK1/2 levels, whereas PGC-1α levels were reduced, confirming apoCIII effects in vivo. Finally, incubation ...
Compounds. Compound I [IUPAC name: N-(3-fluoro-4-((7-methoxy-4-quinolinyl)oxy)phenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide] was synthesized at Amgen, Inc. The MAPK/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2) inhibitor U0126 was obtained from Calbiochem.. Cells. KATOIII (gastric), PC3 (prostate), HT-29 (colorectal), Colo205 (colorectal), BxPC3 (pancreatic), and U-87 MG (glioblastoma) cancer cell lines were obtained from the American Type Culture Collection. NIH3T3 TPR-Met or NIH3T3 RON cells were generated by stable transfection of TPR-Met, a constitutively active, ligand-independent form of c-Met ( 31) or wild-type RON in NIH3T3 cells. Cells were grown as monolayers using standard cell culture conditions.. Antibodies and reagents. Antibodies against c-Met (C-12), RON (C-20), and actin (1615-R) were acquired from Santa Cruz Biotechnology. Antibodies against phospho-c-Met (Y1234/1235), phospho-Gab1 (Y627), phospho-ERK1/2 ...
Extracellular signal-regulated kinase (ERK)-2 is presumed to play an important role in the development of post-traumatic joint contractures. Using a rat injury model, we investigated whether treatment with ERK2 small interfering RNA (siRNA) could reduce the extent of joint capsule fibrosis after an induced injury. Rats were separated into three groups (n = 32 each): non-operated control group, operated contracture group and contracture-treatment group. Stable post-traumatic joint contracture was created through surgical intra-articular joint injury followed by eight weeks of immobilization. In the contracture-treatment group, the rats were treated with lentivirus (LV)-mediated ERK2 siRNA at days 3 and 7 post-surgery. The posterior joint capsule was assessed by western blotting, immunohistochemistry and biochemical analysis for changes in ERK2, phosphorylated (p)-ERK2, myofibroblast, total collagen and relative collagen Type III expression level. Biomechanical testing was used to assess the development
Fingerprint Dive into the research topics of Dopamine D2 receptor stimulation of mitogen-activated protein kinases mediated by cell type-dependent transactivation of receptor tyrosine kinases. Together they form a unique fingerprint. ...
We investigated in IMR90 cells the effects of N-formyl-Met-Leu-Phe (N-fMLP) and WKYMVm (W peptide) on activation of the NADPH oxidase-like enzyme. In serum-deprived human fibroblasts, exposure to 100 microM N-fMLP or 10 microM peptide W for 1 min induced both p47phox translocation and NADPH-dependent superoxide generation. These effects were in large part mediated by prevention of the rapid activation of extracellular signal-regulated kinases (ERKs) by preincubation with the MEK1 inhibitor PD098059. Furthermore, responses to N-fMLP or W peptide were inhibited by pertussis toxin, suggesting the involvement of a seven-transmembrane G protein-coupled receptor(s) for peptides. RT-PCR experiments demonstrated the expression in these cells of the low-affinity receptor FPRL1, but not the high-affinity receptor FPR. Incubation with radiolabeled WKYMVm, which had a higher efficiency on FPRL1, revealed that human fibroblasts express binding sites for 125I-WKYMVm that are specifically displaced by ...
Constitutive activation of the mitogen-activated protein kinase (MAPK) pathway is implicated in the development and progression of many human cancers, including
Söderström T.S., Poukkula M., Holmström T.H., et al. Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8. (англ.) // J. Immunol. (англ.)русск. : journal. - 2002. - Vol. 169, no. 6. - P. 2851-2860. - PMID 12218097. ...
Low temperature is one of the most common environmental stresses affecting plant growth and agricultural production. The mitogen-activated protein kinase (MAPK) cascade plays a pivotal role in...
Fingerprint Dive into the research topics of Involvement of mitogen-activated protein kinase in hippocampal long-term potentiation. Together they form a unique fingerprint. ...
Although several multiprotein complexes containing MAPKs (mitogen-activated protein kinases) have been identified using overexpression of kinases and scaffold proteins, the components of the complexes and their physical properties at endogenous expression levels have not been defined. We characterized a large protein complex containing a nerve-growth-factor-activated ERK (extracellular-signal-regulated kinase) and MEK (MAPK/ERK kinase) in rat pheochromocytoma (PC12) cells. This protein complex fractionated into a high-speed pellet and was resistant to non-ionic detergent treatments that solubilized membranes. Disruption of protein-protein interactions by treatment with high salt was required to facilitate immunoprecipitation of active ERK1 and co-precipitation of MEK1. Microtubule fragments were also present in the detergent-resistant high-speed pellet, and some kinases were bound to them, especially ERK1b (an alternatively spliced isoform of ERK1), which showed a strong preference for binding ...
A novel role of differentiation-inducing factor-1 in Dictyostelium development, assessed by the restoration of a developmental defect in a mutant lacking mitogen-activated protein kinase ERK2 ...
We also took aliquots treated identically to those of Fig. 1A but, instead of blotting the samples, we washed them into MAP kinase buffer and measured the activities of the GST-hERK1 aliquots against a myelin basic protein (MBP) substrate. The results from one representative experiment are shown in Fig. 1B, beneath the relevant gel lane, together with the quantitated activities. Recombinant GST-hERK1 itself had very little activity (Fig. 1B, lane 1), which remained the same after incubation in sea urchin extract (Fig. 1B, lane 2). However, when activated with MEK alone for 1 hour, it showed around a tenfold activation over baseline (Fig. 1B, lane 3). Addition to the sea urchin embryo extract and incubation for 15 minutes at room temperature elevated the activity of the recombinant kinase a further tenfold (Fig. 1B, lane 4). A fivefold increase in the amount of the cell extract (to 75 μg total protein) did not increase the activity of the aliquot (not shown), indicating that soluble factors were ...
Yan Z, Ohuchida K, Fei S, Zheng B, Guan W, Feng H, Kibe S, Ando Y, Koikawa K, Abe T, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Hashizume M, Nakamura M. Inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis. J Exp Clin Cancer Res. 2019 May 27; 38(1):221 ...
4z9l_A mol:protein length:364 Mitogen-activated protein kinase 10 MASKSKVDNQFYSVEVGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLS RPFQNQTHAKRAYRELVLMKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQ VIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTA GTSFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMVRHKILFPGRDYIDQWN KVIEQLGTPCPEFMKKLQPTVRNYVENRPKYAGLTFPKLFPDSLFPADSEHNKLKASQA RDLLSKMLVIDPAKRISVDDALQHPYINVWYDPAEVEAPPPQIYDKQLDEREHTIEEWK ELIYKEVMNS >4z9l_A mol:protein length:364 Mitogen-activated protein kinase 10 MASKSKVDNQFYSVEVGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLS RPFQNQTHAKRAYRELVLMKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQ VIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTA GTSFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMVRHKILFPGRDYIDQWN KVIEQLGTPCPEFMKKLQPTVRNYVENRPKYAGLTFPKLFPDSLFPADSEHNKLKASQA RDLLSKMLVIDPAKRISVDDALQHPYINVWYDPAEVEAPPPQIYDKQLDEREHTIEEWK ELIYKEVMNS ...
Although extracellular signal-regulated kinase (ERK) ? has been shown for its necessity for a variety of the Raf/MEK/ERK pathway signaling its sufficiency in mediating the pathway signaling has not been firmly established. promote ERK autophosphorylation is sufficient to induce growth arrest and differentiation whereas ERK2-I84A and ERK2-R65S/D319N are not as effective. When compared to the […]. ...
Importantly, this work underscores the significance of ERK-dependent signaling in TAA development in MFS. ERK-dependent signaling has been demonstrated previously to contribute to aortic dilation in MFS (18, 20). ANG stimulates ERK1/2 activation via the AT1aR and both Gq proteins as well as βarr2. ERK activated via these different transducers is both spatially and temporally distinct (3) with unique functional outcomes (22, 34). Whereas βarr2-dependent ERK activation appears to lead to TGF-β-independent, proaneurysmal signaling, ANG-stimulated activation of TGF-β signaling has been reported previously to involve Gq proteins (35). Interestingly, G protein- and βarr2-dependent ERK1/2 activation has been shown to require EGFR transactivation in VSMC (21), suggesting the EGFR could serve as a mediator of AT1aR-mediated pathogenic signaling in MFS. This hypothesis is supported by our preliminary work demonstrating a reduction in aortic dilation in FbnC1039G/+ mice treated with the EGFR inhibitor ...
ERK1 (phospho Thr202) + ERK2 (phospho Thr185) antibody (mitogen-activated protein kinase 3) for WB. Anti-ERK1 (phospho Thr202) + ERK2 (phospho Thr185) pAb (GTX52319) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
ERK1 / ERK2, 0.1 mg. The activation of signal transduction pathways by growth factors, hormones and neurotransmitters is mediated through two closely related MAP kinases, p44 and p42, designated extracellular-signal related kinase 1 (ERK 1) and ERK 2,
Roche was developing RG 7167 (also called RO 4987655), an orally active, small-molecule, mitogen-activated ERK-kinase (MEK) inhibitor, for the treatment of