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 ...
S. Xie*, B. Schurink, F. Wolbers, R. Luttge*, and G. Hassink. Nanoscaffolds stiffness affects primary cortical cell network formation. J. Vac. Sci. Technol. B. 2014, 32(6), 06FD03.. S. Xie*, R. Luttge*. Imprint lithography provides topographical nanocues to guide cell growth in primary cortical cell culture. Microelectron. Eng. 2014, 124, 30-36.. Xie, S. J.; Lu, Y. X.; Zhang, S. C.; Wang, L.D.; Zhang X.R.*. Electro-optical gas sensor based on a planar light-emitting electrochemical cell microarray, Small. 2010, 6(17), 1897-1899.. Xiaoyan Wang, Kenichi Harimoto,Sijia Xie, Hao Cheng, Jing Liu, and Zhao Wang*. Matrix Protein Biglycan Induces Osteoblast Differentiation through Extracellular Signal-Regulated Kinase and Smad Pathways. Biol. Pharm. Bull. 2010, 33(11) 1891-1897. ...
p38 Mitogen-Activated Protein Kinases;Tumor Necrosis Factor-alpha;Extracellular Signal-Regulated MAP Kinases;Interferon-gamma;Nitric Oxide;Microglia;Astrocytes;RNA, Messenger;Reverse Transcriptase Polymerase Chain Reaction;MAP Kinase Signaling ...
p38 Mitogen-Activated Protein Kinases;Tumor Necrosis Factor-alpha;Extracellular Signal-Regulated MAP Kinases;Interferon-gamma;Nitric Oxide;Microglia;Astrocytes;RNA, Messenger;Reverse Transcriptase Polymerase Chain Reaction;MAP Kinase Signaling ...
However, the results presented in Fig. 7E, and the observation that Tpl2 overexpression increases ERK1/2 activity (32), suggest that Tpl2 expression could be rate-limiting for the activation of ERK pathway ...
The extracellular-signal-regulated kinase (ERK) pathway is one of the major signaling cassettes of the mitogen activated protein kinase (MAPK) signaling ..
TY - JOUR. T1 - Lithium protection of phencyclidine-induced neurotoxicity in developing brain. T2 - The role of phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways. AU - Xia, Yan. AU - Wang, Cheng Z.. AU - Liu, Jie. AU - Anastasio, Noelle. AU - Johnson, Kenneth M.. PY - 2008/9. Y1 - 2008/9. N2 - Phencyclidine (PCP) and other N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to be neurotoxic to developing brains and to result in schizophrenia-like behaviors later in development. Prevention of both effects by antischizophrenic drugs suggests the validity of PCP neurodevelopmental toxicity as a heuristic model of schizophrenia. Lithium is used for the treatment of bipolar and schizoaffective disorders and has recently been shown to have neuroprotective properties. The present study used organotypic corticostriatal slices taken from postnatal day 2 rat pups to investigate the protective effect of ...
In the present study, we established a novel function for LX acting on a previously unappreciated cell target, namely, human T cells. Both 15-epi-LXA4 and LXB4 inhibited TNF-α secretion from PBMC stimulated by anti-CD3 Abs. We also found that stable analogs of 15-epi-LXA4 and LXB4, namely, ATLa1, ATLa2, and 5-(R/S)-methyl-LXB4, each share this activity and inhibit TNF-α secretion to a similar extent as their corresponding origins, implying that these analogs could be used for improved in vivo treatment of T cell-mediated inflammation. Most results obtained to date indicate that TNF-α, which is produced by T cells upon stimulation by Ags, is also critical for the establishment of chronic inflammatory disorders such as arthritis, inflammatory bowel disease, and others (20, 37), and therefore serves as a primary target for therapeutic intervention (21, 38). Of interest, TNF-α also plays a role in the resolution phase of inflammation (18, 39), rendering the regulation of its bioavailability an ...
Although classic genetic analyses, such as those described above, have revealed much about the molecular pathways involved in artery-vein specification, such approaches have limitations when it comes to examining signaling pathways that function at multiple stages in development. With a typical nonconditional mutation, the primary role for a gene at later stages of development is often difficult to distinguish from indirect consequences of disrupting the gene at an earlier stage. The Hedgehog pathway, for example, plays a critical role in vasculogenesis, but is also involved in development of numerous other structures at various developmental time points.34 Moreover, classic genetic approaches can be hampered by genetic redundancy.35 A powerful alternative approach, chemical genetic analysis, can overcome the challenges posed by repeated utilization of a signaling pathway during development and by genetic redundancy. Recently, Hedgehog signaling inhibitor cyclopamine was instrumental in ...
The RAS/ERK pathway has been intensely studied for about three decades, not least because of its role in human pathologies. ERK activation is observed in the majority of human cancers; in about one-third of them, it is driven by mutational activation of pathway components. The pathway is arguably one of the best targets for molecule-based pharmacological intervention, and several small-molecule inhibitors are in clinical use. Genetically engineered mouse models have greatly contributed to our understanding of signaling pathways in development, tissue homeostasis, and disease. In the specific case of the RAS/ERK pathway, they have revealed unique biological roles of structurally and functionally similar proteins, new kinase-independent effectors, and unsuspected relationships with other cascades. This short review summarizes the contribution of mouse models to our current understanding of the pathway. ...
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.. ...
Abl interactor 1 also known as Abelson interactor 1 (Abi-1) is a protein that in humans is encoded by the ABI1 gene. Abl interactor 1 has been found to form a complex with EPS8 and SOS1, and is thought to be involved in the transduction of signals from Ras to Rac. In addition, the encoded protein may play a role in the regulation of EGF-induced Erk pathway activation as well as cytoskeletal reorganization and EGFR signaling. Several transcript variants encoding multiple isoforms have been found for this gene. Abi1 is adaptor protein. It interacts with c-Abl and WAVE2 which is an actin polymerization regulator. It is known that Abi1 enhances the phosphorylation of WAVE2 by c-Abl. The phosphorylation of c-Abl promotes actin polymerization. Furthermore, Abi1 is a component of the WAVE complex. Some research has shown that knockdown of Abi1 by siRNA promoted degradation of WAVE complex proteins.[citation needed] ABI1 has been shown to interact with ENAH, NCKAP1, EPS8, and SOS1. GRCh38: Ensembl ...
Multiple signaling proteins are activated in pancreatic duct cell carcinogenesis including those associated with the ERK, PKB/AKT, mTOR and STAT3 pathways. The ERK pathway activation appears also increased in duct epithelia adjacent to carcinoma, suggesting tumor micro-environmental effects.
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 ...
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Figure 2: Examples of the probability distribution (a, b, and c) and trace plots (d, e, and f) of reaction rates 2 (which indicates the simultaneous recruitment of Shc and Grb2-SOS complex from the cytosol to the cell membrane by the recruitment of EGFR (a and d)), 16 (which shows the activation of MEK proteins by active Raf (b and e)), and 38 (which refers to the dissociation of active ERK and RSK complex (c and f)) of Model 2 under ...
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
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Influence of caffeine and hyaluronic acid on collagen biosynthesis in human skin fibroblasts Magdalena Donejko,1 Andrzej Przylipiak,1 Edyta Rysiak,2 Katarzyna Gluszuk,2 Arkadiusz Surazynski2 1Department of Esthetic Medicine, 2Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Bialystok, Bialystok, Poland Aim: The aim of this study was to evaluate the effect of caffeine on collagen biosynthesis in human skin fibroblasts and the influence of hyaluronic acid (HA) on this process. Materials and methods: Collagen, [3H]-thymidine incorporation, and prolidase activity were measured in confluent human skin fibroblast cultures that had been treated with 1, 2, and 5 mM caffeine and with caffeine and 500 µg/mL HA. Western immunoblot analysis was performed to evaluate expression of ß1-integrin receptor, insulin-like growth factor receptor phospho-Akt protein and mitogen-activated protein kinase (phospho-extracellular signal-regulated kinase). Results: Caffeine inhibited collagen
TY - JOUR. T1 - Epidermal Growth Factor-Activated Extracellular Signal-Regulated Kinase Suppresses Growth Hormone Expression and Stimulates Proliferation in MtT/E Cells. AU - Nogami, H.. AU - Soya, H.. AU - Hiraoka, Y.. AU - Aiso, Sadakazu. AU - Hisano, S.. PY - 2012/2/1. Y1 - 2012/2/1. N2 - The mechanism for the inhibition of growth hormone (GH) expression by the epidermal growth factor (EGF) was examined in two clonal cell lines, MtT/E and MtT/S. The former has a negligible basal level of GH, whereas the latter has a high basal GH. The treatment of MtT/E cells with retinoic acid resulted in a significant increase in GH mRNA and subsequently GH. This stimulatory response to retinoic acid was strongly suppressed by EGF. This suppression was associated with an increase in the phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk1/2). The MEK [mitogen-activated protein kinase (MAPK) kinases that activate ERK1 and ERK2] inhibitor, PD98059, clearly inhibited the phosphorylation of ...
Antisera. Primary murine monoclonal antibodies included mouse anti-human Hsp90α/β SPA-830 (Stressgen, Victoria, British Columbia, Canada) and D01, a mouse anti-p53 mouse monoclonal antibody recognizing wild-type and mutant p53 (Santa Cruz Biotechnology, Santa Cruz, CA). The primary rabbit polyclonal antisera included antibodies to human ER-α (sc-7207; Santa Cruz Biotechnology), Akt (9272; Cell Signaling Technology, Beverly, MA), phosphorylated Akt (pAkt) recognizing phosphorylated Ser473 (9271; Cell Signaling Technology), Akt phosphosubstrate antibody recognizing the motif (R/K)X(R/K)XX(pT/pS) (9611; Cell Signaling Technology), extracellular signal-regulated kinase (9102; Cell Signaling Technology), phosphorylated extracellular signal-regulated kinase antibody recognizing phosphorylated Thr202 and Thr204 (9101; Cell Signaling Technology), Hsp90α (SPS771; Stressgen), Rb (554136; Becton Dickinson, San Jose, CA), phosphorylated Rb (pRb; 9308; Cell Signaling Technology), CDK2 (sc-163; Santa Cruz ...
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. ...
Inhibition of the Raf/MEK/ERK pathway is sufficient to partially restore CD24 mRNA but not protein expression in RasV12 cells. (A-C) RasV12 cells were treated
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 […]. ...
Aronov A.M., Baker C., Bemis G.W., Cao J., Chen G., Ford P.J., Germann U.A., Green J., Hale M.R., Jacobs M., Janetka J.W., Maltais F., Martinez-Botella G., Namchuk M.N., Straub J., Tang Q., Xie X.. The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.. J. Med. Chem. 50:1280-1287(2007) [PubMed] [Europe PMC] ...
Diabetic patients are prone to developing Alzheimers disease (AD), in which microglia play a critical role. However, the direct effect of high glucose (HG) on microglia and the role of extracellular-signal-regulated kinase 5 (ERK5) signaling in this interaction have not been examined before. Here, these questions were addressed in microglia cultured in HG versus normal glucose (NG) conditions. Initially, HG induced microglial differentiation into the M2a phenotype with concomitant ERK5 activation. However, longer exposure to HG further induced differentiation of microglia into the M2b-like phenotype, followed by the M1-like subtype, concomitant with a gradual loss of ERK5 activation. BIX021895, a specific inhibitor of ERK5 activation, prevented M2a- differentiation of microglia, but induced earlier M2b-like polarization followed by M1-like polarization. Transfection of microglia with a sustained activated form of MEK5 (MEK5DD) prolonged the duration of the M2a phenotype, and prevented later
Tumors with mutant BRAF or mutant KRAS are dependent on ERK signaling and are sensitive to inhibitors of the pathway. Selective RAF, MEK and ERK inhibitor have...
The expression of CD47 on the cancer cell surface transmits "dont eat me" signalling that not only inhibits phagocytosis of cancer cells by phagocytes but also impairs anti-cancer T cell responses.
Gentaur molecular products has all kinds of products like :search , GenWay \ SRE Reporter Kit (MAPK ERK Signaling Pathway ) \ GWB-PS60EE for more molecular products just contact us
Three-tiered kinase modules, such as the Raf-MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase)-ERK (extracellular signal-regulated kinase) mitogen-activated protein kinase pathway, are widespread in biology, suggesting that this structure conveys evolutionarily advantageous properties. We show that the three-tiered kinase amplifier module combined with negative feedback recapitulates the design principles of a negative feedback amplifier (NFA), which is used in electronic circuits to confer robustness, output stabilization, and linearization of nonlinear signal amplification. We used mathematical modeling and experimental validation to demonstrate that the ERK pathway has properties of an NFA that (i) converts intrinsic switch-like activation kinetics into graded linear responses, (ii) conveys robustness to changes in rates of reactions within the NFA module, and (iii) stabilizes outputs in response to drug-induced perturbations of the amplifier. These properties ...
The HER-2 oncogene, a member of the erythroblastosis oncogene B (ERBB)-like oncogene family, has been shown to be amplified in many types of cancer, including breast cancer. However, the molecular mechanism of HER-2 overexpression is not completely understood. The phosphorylation of proteins on the serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is specifically catalyzed by the prolyl isomerase Pin1 and is a key signaling mechanism in cell proliferation and transformation. Here, we found that Pin1 interacts with mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) protein kinase 1, resulting in the induction of HER-2 expression. Pin1−/− mouse embryonic fibroblasts exhibited a decrease in epidermal growth factor (EGF)-induced MEK1/2 phosphorylation compared with Pin1+/+ mouse embryonic fibroblast. In addition, a knockdown of Pin1 resulted in the inhibition of MEK1/2 phosphorylation induced by EGF in MCF-7 cells. Furthermore, PD98059, ...
Stimulation of the Ras pathway results in the activation of ERK and RSK, but the precise mechanisms involved in RSK activation and inactivation remain elusive. In this study, we characterized the ERK binding domain of RSK1 and found that a serine residue located near the docking site (position 749 in avian RSK1) was involved in the regulation of ERK1/2 binding (Fig. 1 to 3). We also found that Ser749 was efficiently phosphorylated by the RSK1 N-terminal kinase domain in vitro (Fig. 4) and that mutations in the RSK1 kinase domains disrupted ERK dissociation (Fig. 5). Analysis of different RSK isoforms revealed that RSK1 and RSK2 activation induced ERK1/2 release but that mitogen stimulation did not affect the interaction of ERK1/2 with RSK3 (Fig. 6). We also found that RSK3 remains activated longer than RSK1 and RSK2 (Fig. 7), indicating that ERK association promotes RSK activation or antagonizes RSK inactivation.. Our results indicate that the minimal region in RSK1 necessary for ERK1/2 docking ...
Several studies have shown that ERK in the ACC is activated and contributes to the affective aspect in the inflammatory and phantom pain.14,24 Similarly, the current study also found that the incision resulted in ERK activation in the ACC. However, the incision-evoked ERK activation is biphasic and different from those in inflammatory pain or neuropathic pain. The activation pattern of p-ERK in formalin-induced inflammatory pain is still not fully determined. In a recent study by Wei and Zhuo, p-ERK in the ACC was observed to be transiently up-regulated in the formalin test.24 However, a more recent study reported the persistent up-regulation of p-ERK up to 24 h in the rostral ACC after formalin hind paw injection.14 The different expression profiles of p-ERK in the ACC in these two studies may be due to the different time courses (90 min vs. 24 h) and subregions of ACC. Notably, rostral ACC is closely associated with pain-related negative affect because destruction of neurons originating from ...
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 ...
Primary antibodies used were rabbit or guinea pig anti-DGKζ (K. Kim et al., 2009), mouse anti-PKCα (BD Biosciences), mouse (Sigma), rabbit (Sigma), or guinea pig (Synaptic Systems) anti-calbindin, mouse anti-metabotropic glutamate receptor 1 (mGluR1, BD Biosciences), mouse anti-FLAG (M2, Sigma), rabbit anti-synapsin 1/2 (Synaptic Systems), mouse anti-β-actin (Santa Cruz Biotechnology), rabbit anti-mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/Erk, Cell Signaling Technology), rabbit anti-phosphorylated MAPK (Cell Signaling Technology), rabbit anti-GluA2 (Millipore), rabbit anti-PICK1 (Abcam), and rabbit anti-PSD-93/chapsyn-110 (1634) (M.H. Kim et al., 2009) antibodies. Secondary antibodies used were HRP-conjugated anti-mouse or anti-rabbit IgG (GE Healthcare), HRP-conjugated anti-guinea pig IgG (Jackson ImmunoResearch Laboratories), AlexaFluor-647-conjugated anti-mouse IgG (Jackson ImmunoResearch Laboratories), AlexaFluor-647-conjugated anti-rabbit IgG ...
Sigma-Aldrich offers abstracts and full-text articles by [Qi Zhang, Liang Wei, Hongchuan Yang, Wanqi Yang, Qingyu Yang, Zhuofan Zhang, Kailang Wu, Jianguo Wu].
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each group). Ultrastructure features in normal group ((a) ×4000, (b) ×8000, (c) ×10000), model group ((d) ×4000, (e) ×8000, (f) ×8000), PC6 group ((g) ×6000, (h) ×8000, (i) ×8000), and LI4 group ((j) ×5000, (k) ×8000, (l) ×8000). Cardiocyte and micrangium ((a, d, g, j), ×4000~6000), myofibril, I band, and Z-line ((b, e, h, k), ×8000), intercalated disc ((c,f,i, l), ×8000~10000). Some changes of the ultrastructure: mitochondria swelling ((d, e), cell apoptosis (j), endothelial cell interstitial hyperplasia (d), muscle plasma nets expansion (e), out-sync contraction of contraction band ((e, j), and intercalated disc deformation ((f, i, l). With reference to normal group, compared EA group with model group, EA significantly reduced cardiac muscular tissue damage ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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 ...
Oncotarget | https://doi.org/10.18632/oncotarget.27335 Thomas B. Davis, Mingli Yang, Heiman Wang, Changgong Lee, Timothy J. Yeatman, W. Jack Pledger
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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 ... ...
View Human/Mouse Phospho-ERK1 (ERK1 T202/Y204, ERK2 T185/Y187) Antibody 1088B (MAB18251) datasheet. Validated in Simple Western, WB
Extracellular signal-regulated kinases(ERKs), belonging to the family of mitogen-activated protein kinases (MAPKs), are cytoplasmic and nuclear serine/threonine kinases involved in the signal transduction of several extracellular effectors. Recent evidence indicates the presence of p21 Ras and the phosphorylation of ERK1 and ERK2, suggesting the occurrence of the Ras/ERK cascade in mammalian spermatozoa. The present article describes the biological role of ERK during the acrosome reaction of human spermatozoa on stimulation with zona pellucida (ZP). The mitogen-activated protein-kinase inhibitor PD098059 was used as a pharmacological tool to study the involvement of extracellular signal-regulated kinases in the induction of the acrosome reaction in human spermatozoa. This compound significantly inhibited the acrosome reaction induced by both ZP and the calcium ionophore A23187. These results suggest that ERKs are involved in the signal trans-duction pathway through which ZP stimulation works ...
Phosphoprotein signalling pathways have been intensively studied in vitro, yet their role in regulating tissue homeostasis is not fully understood. In the skin, interfollicular keratinocytes differentiate over approximately 2 weeks as they traverse the epidermis. The extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) pathway has been implicated in this process. Therefore, we examined ERK-MAPK activity within human epidermal keratinocytes in situ. We used confocal microscopy and immunofluorescence labelling to measure the relative abundances of Raf-1, MEK1/2 and ERK1/2, and their phosphorylated (active) forms within three human skin samples. Additionally, we measured the abundance of selected proteins thought to modulate ERK-MAPK activity, including calmodulin, β1 integrin and stratifin (14-3-3σ); and of transcription factors known to act as effectors of ERK1/2, including the AP-1 components Jun-B, Fra2 and c-Fos. Imaging was performed with sufficient
We have already reported that the activation of extracellular signal-regulated kinase (Erk) is critical in the stimulation of cell proliferation during the promotion stage of urethane-induced lung tumorigenesis in mice. Also, we have found that vitamin E suppresses lung tumorigenesis by inhibiting cell proliferation at the promotion stage. However, it is still unclear whether this inhibitory effect at the promotion stage is based on the antioxidative effect of vitamin E or not. In order to address this question, we examined the inhibitory effect of α-tocopheryloxybutyric acid (TSE), an ether derivative of vitamin E that cannot act as an antioxidant in vivo, on cell proliferation and the activation of Erk during promotion of lung tumorigenesis. On day 30 after urethane injection (750 mg/kg, i.p.) in A/J mice, TSE or vitamin E at 100 μmol/kg, p.o. was administered. Twenty-four hours after the final administration, the mice were killed to analyze cell proliferation and related parameters. The ...
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 ...