IndraLab
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"Mechanistically, KDM6A knockout abolished NGF-induced activation (phosphorylation) of Akt and ERK1/2 (Figure xref C), which are known to be involved in NGF-mediated protection of CML cells against imatinib xref , whereas re-expression of wild-type KDM6A or introduction of the KDM6A-ED mutant re-enabled NGF to trigger activation of Akt and ERK1/2 in K562 cells with KDM6A knocked out (Figure xref D)."
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"Use of PD98059, a specific inhibitor of MEK1 located upstream of extracellular signal regulated kinases (ERKs), revealed that the NGF- and MPTP induced proliferative effect depends on the MEK1 pathway because PD98059 diminished the proliferation completely, and interestingly, NGF and MPTP promoted sustained activation of ERKs."
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"Our model predicts that normal EGFR signalling results in a transient ERK signal due to receptor degradation, NGF signalling results in a sustained ERK signal (via the Rap1 pathway) as there is no degradation of the TrkA receptor, and cancerous EGFR signalling results in a constitutive and sustained ERK signal (via the Rap1 pathway) because receptor degradation is either abolished or counteracted."
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"Analysis of calcium and calmodulin involvement in NGF-induced activation of Erk1/2 revealed a calcium and calmodulin-dependent inhibition of sustained phosphorylation in Nogo-A-overexpressing cells but not in wild type cells, suggesting that Nogo-A facilitated the activation of calcium/calmodulin to alter NGF signaling."
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"Thus, the same regulatory molecules induced by DEX represent negative-feedback regulators of EGF receptor signaling.In support of a possible suppressive cross-talk between DEX and TrkA, it has been demonstrated that NGF signaling upregulates Erk-specific dual-specificity phosphatases, DUSPs, thereby leading to reduced Erk1/2 phosphorylation and constituting a negative-feedback loop for the prevention of axon overgrowth (Camps et al., 1998; Peinado-Ramon et al., 1998; Finelli et al., 2013)."
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"Based on the fact that DEX has been described as a potent inhibitor of the biological effects of neurotrophins, and in our previous observation indicating that Sprouty4, is induced by DEX in neuronal cells, we proposed that the induction of Sprouty4 by DEX pretreatment could translate into a strong inhibition of the NGF/TrkA downstream signaling pathway.In order to analyze whether the DEX-induced expression of Sprouty4 could be responsible of the DEX inhibitory effects on neurotrophin signaling, we decided to analyze NGF-induced Erk/MAPK activity in PC12 cells transfected with either Sprouty4-shRNA-GFP or control-shRNA-GFP and pretreated with DEX (Figure 2A)."
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"Recent studies show that the compounds in the ginger rhizome significantly enhance cognitive functioning in the brain of healthy mice and those with cognitive impairments such as Alzheimer’s. Ginger has also been shown to improve cognitive function by activating the ERK/CREB pathway induced by increased hippocampal NGF levels (
Lim et al., 2014)."
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"Dynamics in ERK signalling have first been described in the PC12 cell line, in which both growth factors EGF and NGF activate ERK signalling, but with different dynamics and lead to different cellular outcomes, i.e. cell proliferation or differentiation, respectively (see above, Figure 1B) [17,202]."
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"At the single-cell level, however, a mix of transient, oscillatory, and sustained ERK activity trajectories were observed (Fig XREF_FIG F-H, XREF_SUPPLEMENTARY), showing that EGF- and NGF induced ERK activation kinetics are the result of heterogeneous cell responses distinct from the population average."
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"Specifically, we have not observed any correlation between biosensor expression levels and NGF triggered ERK activity at 40 ' after stimulation, a time point and experimental condition at which highly heterogeneous ERK activity is observed in the cell population (XREF_SUPPLEMENTARY)."
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"Considering that all pulsed NGF stimulation conditions led to an identical 1 st ERK activity peak implies the existence of (i) a slight delay in the activation of the NGF evoked positive feedback and (ii) an additional regulation of the ERK-Raf positive feedback strength, which would explain the induction of adaptive or sustained ERK activation."
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"The persistence of NGF mediated activation of Erk signaling may be dictated, in part, by the ability of TrkA receptors to sustain activity within the acidic environment of endosomes [XREF_BIBR, XREF_BIBR], and also by a delay in the transition from early to late endosomes and lysosomes [XREF_BIBR]."
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"The ELISA results revealed that NGF significantly promoted the production and secretion of VEGF in Muller cells after 12 or 24 h of stimulation, with more elevation after 24 h. Furthermore, NGF activated ERK1/2 and PI3K and AKT signaling, which was shown by the marked upregulation of phosphorylation in the western blot."
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"Overexpression of either wild type or mutant SH2-Bbeta(R555E) did not alter tyrosyl phosphorylation of TrkA, Shc, or phospholipase Cgamma in response to NGF or NGF-induced activation of ERK1/2, suggesting that SH2-Bbeta may initiate a previously unknown pathway(s) that is essential for NGF-induced neurite outgrowth."
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"Previous studies have shown that NGF increases ERK phosphoylation through activation of Ras, thus the ability of Ras (17N) to attenuate pERK in the sensory neuronal cultures grown in 30 ng/ml NGF demonstrates that the infection with dominant negative Ras suppresses Ras activity (XREF_FIG)."
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"Given this and the structural features conferred by the coiled-coil domains [ xref ], together with our functional data, it is tempting to speculate that NECC2 might act as a scaffolding factor facilitating the interaction of the signaling molecules responsible of NGF-dependent persistent ERK activation."
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"Analysis of calcium and calmodulin involvement in NGF-induced activation of Erk1/2 revealed a calcium and calmodulin-dependent inhibition of sustained phosphorylation in Nogo-A-overexpressing cells but not in wild type cells, suggesting that Nogo-A facilitated the activation of calcium/calmodulin to alter NGF signaling."
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"Although it has not been determined whether Erk signaling mediates CSPG function, nerve growth factor (NGF) promoted growth of conditioning DRG neurons cultured on CSPGs xref , suggesting a potential connection between the downstream activation of Erk by NGF and its neutralization of CSPG- mediated growth suppression."
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"Although Shoc2 overexpression in PC12 cells had no effect on NGF-stimulated neurite outgrowth, probably due to the highly sustained NGF-dependent ERK activation in these cells xref , xref , xref , Shoc2 knockdown significantly reduced both NGF-induced ERK activation and neurite outgrowth."
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"In the present study, we examined the influence of DHEA on nerve growth factor (NGF)-mediated survival in serum deprived PC12 cells and analyzed the influence of DHEA on NGF induced ERK1/2 mitogen activated protein (MAP) kinase activation by enzyme linked immunosorbent assay (ELISA)."
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"Because activation of the MEK/ERK pathway contributes to the axon growth response to NGF ( xref ; xref ; xref ) and is an essential step in the axon growth response of sympathetic neurons to TNFR1-activated TNFα-mediated reverse signalling ( xref ), we investigated whether TWE-PRIL/APRIL modulates ERK activation by NGF and whether this plays a role in axon growth suppression by TWE-PRIL reverse signalling."
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"Taken together, the above findings indicate that GITR acts as a co-accessory molecule in NGF–induced ERK activation in neonatal sympathetic neurons in much the same way it does in CD3–stimulated T cells, and that this underlies the selective effect of GITRL–GITR signalling on axonal growth."
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"In those cell systems, EGF induces transient activation of ERK (extracellular signal regulated kinases) whereas NGF and HRG induce sustained activation of ERK, of which the duration is thought to be critical to cell fate determination, and therefore it may induce different gene expression trajectories."
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"In addition, in the medullary thick ascending limb cells of the rat kidney, aldosterone inhibited NHE3 through rapid activation of the ERK signaling pathway and NGF-induced ERK activation inhibited both basal (NHE1 mediated) and apical (NHE3 mediated) surface acid extrusion xref , xref ."
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"The observation that NGF did not alter the voltage dependence of
activation of TTX-S currents in NPY2R and CHRNA3 neurons
was quite unexpected considering that ERK1/2, which supposedly mediates this
effect in IB4 /caps neurons, is also activated by NGF in
CHRNA3 neurons, as we have recently shown, and probably also in NPY2R neurons."
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"Cell differentiation was induced with nerve growth factor (NGF) in an early transient stimulation that induced an extracellular signal regulated kinase (ERK) - and transcription dependent latent process, and a second sustained NGF stimulation driving the fast neurite extension process by ERK- and PI3K dependent activities (XREF_SUPPLEMENTARY)."
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"Because the inhibition of NGF induced neurite outgrowth and Akt/ERK1/2 phosphorylation were both observed with DEX pretreatment, even after the removal of DEX, we propose that the DEX does not directly interact with the NGF TrkA receptor, but instead indirectly impedes the signaling activation of Akt and ERK1/2 by NGF."
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"It has been reported that NGF mediated ERK activation induces phosphorylation of cAMP response element binding protein (CREB), which further recruits the CREB binding protein (CBP) to the promoter regions of cAMP responsive genes associated with dendritic spine growth, morphology change, synaptic plasticity, and long-term memory XREF_BIBR, XREF_BIBR."
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"While both Rit and Rin contribute to NGF mediated activation of ERK- and p38 dependent signaling cascades [XREF_BIBR, XREF_BIBR], Rit dependent p38 activation is required for PACAP38 mediated neurite formation [XREF_BIBR], whereas Rin loss inhibits PACAP38 mediated neuronal differentiation without disrupting MAPK signaling."
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"Although Shoc2 overexpression in PC12 cells had no effect on NGF stimulated neurite outgrowth, probably due to the highly sustained NGF dependent ERK activation in these cells XREF_BIBR, XREF_BIBR, XREF_BIBR, Shoc2 knockdown significantly reduced both NGF induced ERK activation and neurite outgrowth."
sparser
"On the other hand, however, because ERK1/2 can also be activated by NGF and other neurotrophic factors, its inactivation could be a result of PEDF-induced decreases in levels of other neurotrophic molecules and receptors or because of a concerted effect from loss of PEDF and decreased levels of these factors."
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"Nerve growth factor, by binding to the tyrosine protein kinase A receptor on the superior cervical ganglion surface, activates the extracellular regulatory protein kinase (ERK1/2), catalyzes serine phosphorylation at S727 in STAT3, and activates STAT3 along with downstream signaling molecules to facilitate nerve growth (43)."
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"In contrast, nerve growth factor (NGF) triggers sustained ERK activation, leading to cell differentiation.61 Thus, the shift in YAP-SMAD dynamics suggests that ITCH might modulate cellular reactions to TGF-β stimulation, potentially impacting cellular fates such as proliferation or apoptosis."
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"We report here that although FGF, NGF, and EGF all activate mitogen-activated protein (MAP) kinase (extracellular signal-related kinase [ERK]) in rat hippocampal (H19-7) and pheochromocytoma (PC12) cells, the activation of ERK by the neurogenic agents FGF and NGF is dependent upon protein kinase Cdelta (PKCdelta), whereas ERK activation in response to the mitogenic EGF is independent of PKCdelta."
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"Saito et al. have recently reported a temporal correlation between PACAP and NGF stimulation of ERK, and activation of Egr1, based on simultaneous measurement of pERK, pp38, pJNK, pCREB, c-Fos, Egr1, c-Jun, JunB and FosB as a function of time after treatment with NGF and PACAP in PC12 cells [XREF_BIBR]."
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"Although it has not been determined whether Erk signaling mediates CSPG function, nerve growth factor (NGF) promoted growth of conditioning DRG neurons cultured on CSPGs XREF_BIBR, suggesting a potential connection between the downstream activation of Erk by NGF and its neutralization of CSPG- mediated growth suppression."
sparser
"Because the inhibition of NGF-induced neurite outgrowth and Akt/ERK1/2 phosphorylation were both observed with DEX pretreatment, even after the removal of DEX, we propose that the DEX does not directly interact with the NGF TrkA receptor, but instead indirectly impedes the signaling activation of Akt and ERK1/2 by NGF."
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"Further investigation revealed that both stimuli activated the same protein kinase, the extracellular signal regulated kinase (ERK), with a distinct temporal feature -- i.e., EGF induces a transient ERK activation -- whereas NGF triggers a sustained ERK activation [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"4950 Some groups have reported that TGF, nerve growth factor (NGF), platelet-derived growth factor, insulin-like growth factor-I, and basic fibroblast growth factor, all known to be overexpressed in degenerated disk tissue, can stimulate p38/ERK signaling in IVD of various species.515253 Furthermore MMPs, inducible nitric oxide synthase, tissue inhibitor of metalloproteinases, aggrecan, type II collagen, Sox-9, acid-sensing ion channel, and tonicity-responsive enhancer-binding protein have all been identified as target genes of ERK in IVD cells."
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"Overexpression of either wild type or mutant SH2 Bbeta (R555E) did not alter tyrosyl phosphorylation of TrkA, Shc, or phospholipase Cgamma in response to NGF or NGF induced activation of ERK1/2, suggesting that SH2-Bbeta may initiate a previously unknown pathway (s) that is essential for NGF induced neurite outgrowth."
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"NGF stimulated concentration-dependent ERK transcriptional activity with significantly higher potency in cells overexpressing TrkA and NRP1 compared with cells expressing TrkA alone (Figure 6N and Supplemental Table 3; NGF EC : TrkA alone, 214 pM; TrkA + NRP1, 71 pM; paired t test, P = 0.0004)."
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"In the second (61), they showed that, in the case of PC12 cells, EGF induces strong transient ERK activation that leads to cell proliferation, whereas NGF promotes sustained ERK activation, and cell differentiation, EGFR activation, and thus ERK signaling were switched from transient to sustained when receptor internalization was inhibited, mutated, or with impaired dimerization."
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"The simulation program predicted that a rapid increase of EGF or NGF causes transient ERK activation, whereas the final concentration of the growth factors determines the sustained activation level of the intracellular signaling pathway; subsequently the predicted patterns were validated experimentally, demonstrating the power of using simulations to leverage both mathematical theory and experimental results [XREF_BIBR]."
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"By combining the KDE subtraction method with QuAM, which can greatly increase the numbers of investigated and quantified cells, we rendered a fully quantitative analysis of DRG neurons feasible.We quantified and characterized the NGF responsive subgroups and found DRG-subgroup specific differences in dose dependent NGF responsiveness as well as in the magnitude of NGF-induced Erk1/2 signaling."
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"Our present study has generated the following major findings: (i) although RGS14 interacts with a wide array of Ras and Rap isoforms in vitro , the most likely cellular target for full-length RGS14 is activated H-Ras; (ii) the binding of activated H-Ras to RGS14 facilitates assembly of a multiprotein complex with components of the ERK MAPK cascade (B-Raf, MEK1, and ERK1); (iii) loss of RGS14 expression blunts both NGF- and bFGF-promoted neurite outgrowth of PC12 cells; and (iv) duration of ERK activation by NGF and bFGF is shortened by RGS14 knockdown, suggesting a mechanistic explanation for impairment of agonist-promoted neuritogenesis seen upon RGS14 depletion."
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"The sensitization increase during the first hour could theoretically be caused by (i) an increase in the percentage of responsive cells, or by (ii) an increase in the response amplitude of the responsive cells.To study this, we measured the kinetics of 1 nM NGF-induced Erk1/2 activation after incubation for 5, 15, 30 and 60 min and estimated the percentage of responsive cells."
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"Furthermore, the cytokine interleukin 6 (IL-6), as well as NGF, both linked to nociceptive plasticity, were shown to cause ERK and mTOR dependent increases in translation [XREF_BIBR] in DRG neurons, while peripheral nerve injury led to increases in protein synthesis in the sciatic nerve [XREF_BIBR]."
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"Stimulation of PC12 cells with epithermal growth factor (EGF) induces transient ERK activation, which results in proliferation, while nerve growth factor (NGF) stimulation produces sustained ERK activation that leads to differentiation into cells resembling sympathetic neurons [XREF_BIBR, XREF_BIBR]."
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"To determine potential intracellular convergence points for KCl and NGF mediated survival, we examined two downstream substrates; the ERKs (MAP kinases), which are activated in sympathetic neurons by depolarization (Franklin et al. 1995) and by NGF (Creedon et al. 1996), and the serine threonine kinase Akt, which is activated by TrkA (Andjelkovic et al. 1998), and is required for NGF mediated sympathetic neuron survival (Crowder and Freeman 1998)."
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"Additionally, they analyzed additional signaling events and found that hericenone E activates the ERK1/2 and PI3K/Akt cascades independently of the presence of NGF.The stimulation of ERK activity by hericenone E independently of NGF suggests that this compound is involved in additional signaling pathways directly regulated by hericenone E."
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"The high expression of interleukin (IL)-33 can elevate the expression of matrix metallopeptidases (MMP) 2 and 9 in patients with acute lung injury. xref SLC2A6 may be a critical biomarker for predicting survival of sepsis patients. xref V-set immunoglobulin-domain-containing 4 (VSIG4) may be involved in lung injury by inducing phagocytosis. xref Activation of ERK1/2 by NGF1B depends on MAPKKK c-Raf, eventually inducing inflammation."
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"Our results clearly show that, unlike NGF that activates MAPK and ERK and NF-kappaB in two different and redundant pathways, 29 TNFalpha treatment induces NF-kappaB and MAPK and ERK activation in one unique pathway as blocking either component leads to the same biological response, more specifically JNK mediated apoptosis."
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"The kinetics of RTK and ERK signaling is critical to its function, in that the apparently divergent effects of RTK and ERK signaling on proliferation versus differentiation are explained by the ability of Ngf and Ntrk1 to activate ERK in a sustained manner, whereas Fgf induces strong, transient ERK activation."
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"NGF activates the extracellular signal regulated kinase (ERK) mitogen activated protein kinases (MAPKs), which in turn activate the pp90 ribosomal S6 kinase (RSK) family of Ser/Thr kinases, all three members of which were found to catalyze CREB Ser 133 phosphorylation in vitro and in vivo."