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NTRK1 activates ERK. 62 / 63
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"For example, in PC12 cells, activated EGFR rapidly undergoes the clathrin based endocytosis and the following degradation, whereas activation of TrkA, a receptor for NGF, induces its translocation to long lived signalling endosomes, where TrkA avoids degradation and mediates sustained ERK activation 59."
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"Finally, because Trk activates the extracellular signal regulated kinase pathway in Aplysia sensory neurons, we examined whether this pathway mediates the injury induced changes."
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"The mechanism involved TrkA dependent activation of extracellular signal regulated kinase (ERK1/2) but not phosphatidylinositol 3-kinase (PI3K)/Akt, and de novo protein synthesis."
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"To investigate whether trkA activates the Erk1/2 signaling pathway during responses to NGF, cells were incubated 60 min with the Erk1/2-specific inhibitor, PD-98059 (30 lmol/L, apical and basolateral; 9900L, Cell Signaling, Danvers, MA) or DMSO (0.06%)."
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"ApTrkl, a Trk like receptor, mediates serotonin- dependent ERK activation and long-term facilitation in Aplysia sensory neurons."
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"Ntrk1 promoted mesangial cell proliferation and inflammation in MsPGN rats by activating the STAT3 and p38/ERK MAPK signaling pathways."
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"In fact, 85-90% of papillary carcinomas possess RET, NTRK1, BRAF or RAS mutations that induce MEK and ERK signaling."
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"TrkA activated cell death does not require p38, JNK or Erk1/2 kinases but does require activation of class III PI-3 kinase and is blocked by the casein kinase 1 (CK1) inhibitor, D4476."
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"In the present study, we investigated the possible involvement of TrkA in alpha 2 -ARs induced modulation of ERK1/2 and Akt cascades and differentiation."
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"Ras and ERK is activated by sAPPalpha, its secretase ADAM17, and neurotrophin Trk receptors."
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"When exposed to nerve growth factor (NGF), PC12 cells transition from a proliferative to a differentiated state, which is manifested as the induction of neurite outgrowth driven by TRKA mediated activation of the ERK MAP kinase pathway [XREF_BIBR]."
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"The increased p-Erk was mediated by Trk activation, because pretreatment with K252a, a Trk kinase inhibitor, reduced BDNF and H 2 O 2 -induced increases of both p-Trk and p-Erk (XREF_FIG)."
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"However, NGF has been shown to cause trkA activation in 1 min (Kaplan et al. 1991) and maximum Erk activation 1.5 min after exposure (Saragovi et al. 1998)."
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"PD-98059 (30 lmol/L, apical and basolateral) did not itself affect Na + transport, but attenuated the NGF-induced reduction in Na + transport, indicating that trkA activated the Erk 1/2 signaling cascade."
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"Peptidomimetic TrkA agonists with structural similarity to NGF loop 4 have been shown to activate AKT and ERK signaling and provide neuroprotection in cell culture systems [XREF_BIBR]."
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"The mechanism involved TrkA-dependent activation of extracellular signal-regulated kinase (ERK1/2) but not phosphatidylinositol 3-kinase (PI3K)/Akt, and de novo protein synthesis."
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"That said, it is highly likely that they have different sets of miRs compared to primary epithelial ovarian cells.AKT and ERK signalling pathways activated by NGF and TRKA favour cancer cell growth [7]."
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"The nociceptive activity of NGF is mediated through the activation of TrkA and p75NTR receptors on sensory nerve endings and of the corresponding downstream signaling cascades, particularly TrkA-activated Erk and PLC–1γ pathways and p75NTR-mediated c-jun activation [12], [26], [27]."
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"Both EGFR and TRKA induced ERK activation in RCS cells and upregulated the WNT3a mediated Topflash induction (XREF_FIG)."
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"Pertussis toxin treatment did not prevent ramelteon from activating ERK1/2 but pretreatment with a tyrosine kinase (Trk) inhibitor, K252a, did, suggesting that an activation of Trk may mediate melatonin-receptor dependent ERK1/2 activation."
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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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"Use HEK293T cells for TrkA site-dependent ERK activation."
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"Since target innervation of BFCNs is TrkA dependent and the timing of maximal ERK activation in these neurons correlates with the establishment of target innervation, TrkA mediated activation of the ERK pathway may play a crucial role in the maintenance of target innervation by BFCNs."
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"Once in endosomes, TrkA induces the selective activation of ERKs via the small GTPase Rap1 and B-Raf [XREF_BIBR, XREF_BIBR]."
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"Furthermore, the activation of TrkA and TrkB by BDNF and NGF activates Ras, and promotes the activation of extracellular signal regulated kinase (ERK)."
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"In the present study, a possible involvement of TrkA transactivation in the alpha 2 -AR induced sustained activation of MAPK and Akt in PC12 cells was first investigated with the employment of a phosp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Similarly, the administration of ABG001 (tetradecyl 2,3-dihydroxybenzoate), a neuritogenic substance, enhanced the survival and neurite growth of newborn cells in adult hippocampal via TrkA receptor triggered ERK and PI3K-Akt-mTOR signaling pathways, that leads to an enhanced preferential spatial cognitive function."
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"PD-98059 (30 mumol/L, apical and basolateral) did not itself affect Na + transport, but attenuated the NGF induced reduction in Na + transport, indicating that trkA activated the Erk 1/2 signaling cascade."
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"Conversely, in BI-ALCLs and cALCLs there was an enrichment in genes involved in the neurotrophin signaling pathway (NTRK1, NTRK2, NTF3, NGF), which in turn activates the JAK/STAT, PI3K/Akt and MEK/ERK signaling cascades to promote cell proliferation, differentiation and survival [52,53]."
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"NGF mediated TrkA signaling in PC12 cells typically activates Erk1/2 and Akt downstream signaling."
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"Given that stimulation of TrkA by NGF induces auto-phosphorylation of this receptor and promotes ERK1/2 activation, we thought it likely that NGF and TrkA interactions might differentially activate downstream signaling between the 2 phenotypes."
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"Expectedly, the withdrawal of NGF attenuated endogenous TrkA mediated ERK activation; the addition of PACAP rapidly induced ERK phosphorylation to levels that appeared comparable with those from endogenous TrkA activation within the first hour of treatment."
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"In our previous study, we revealed that the L. platyphylla extract contains spicatoside A ( xref ), a steroidal saponin that exerts a neurotrophic effect by inducing neurite outgrowth in PC12 cells and by inducing NGF synthesis in astrocytes through TrkA receptor-mediated PI3-kinase and ERK1/2 activation of CREB, which regulates neuronal function and LTP [ xref ]."
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"TrkA signaling resulted in activation of JNK and ERK (XREF_FIG)."
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"In PC12 cells and primary dorsal root ganglion neurons, RGS12 sustains nerve growth factor (NGF)-driven ERK activity and, therefore, neurite outgrowth by scaffolding a complete MAPK cascade, including the NGF-receptor TrkA, activated H-Ras, B-Raf, MEK2, and ERK proteins XREF_BIBR."
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"This approach allows us to quantify the relative contribution of neuronal subpopulations, culture conditions, and expression levels of signaling proteins to the observed cell-to-cell variability in NGF/TrkA-initiated Erk1/2 signaling."
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"Collectively, these findings suggest that a single substitution (V432E) in the trkA TMD results in a selective impairment of trkA mediated erks signaling pathway."
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"Ntrk1 promotes mesangial cell proliferation and inflammation in rat glomerulonephritis model by activating the STAT3 and p38/ERK MAPK signaling pathways."
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"These data suggest a distinct requirement for CSK in the regulation of NGF and TrkA activation of RAS, RAC, ERK, and AKT via the differential control of SFKs in the orchestration of neuronal differentiation."
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"Furthermore, the data show that even for the population of patches that form associated with mitochondria there are two distinct subpopulations with dedicated roles in the formation of filopodia and fission, respectively.The concentration profile of NGF induced fission on axonal mitochondria is consistent with activation of the TrkA receptor (Kaplan et al., 1991) that activates both PI3K and Erk signaling."
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"Given the NGF-dependent colocalization of NECC2 and TrkA, we examined the effects of Necc2 silencing and overexpression on the phosphorylation rate of the main TrkA-activated effectors, ERK1/2 and Akt, in NGF-treated cells."
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"Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin dependent ERK activation and BTIC growth."
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"NGF treatment induced rapid autophosphorylation of TrkA and increased p-AKT and ERK1/2 in both K562 and 32D cells with endogenous and exogenous expression of TrkA, respectively (XREF_FIG)."
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"Beside the state of activation of TrkA, we decided to analyze downstream signaling pathways that are involved in NGF-mediated pain transmission and perception such as TrkA-activated Erk and PLC–1γ pathways and p75NTR-mediated c-jun activation [12], [26], [27]."
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"Indeed, previous in vitro studies demonstrated that while both TrkA and TrkC receptors activated ERK and Akt pathways, they did so to a different extent, leading to distinct effects on axonal morphology [12]."
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"In PC12 cells, TrkA gene silencing blocked activation of Akt and ERK1/2 in response to LRP1 ligation; however, more work will be necessary to determine which Trk receptors function in LRP1 dependent signaling."
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"At molecular level, our findings indicate that ectopic expression of a mutated form of Spry4 (Y53A), in which a conserved tyrosine residue was replaced, fail to block both TrkA mediated Erk and MAPK activation and neurite outgrowth induced by NGF, suggesting that an intact tyrosine 53 site is required for the inhibitory effect of Spry4 on NGF signaling."
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"In our study, inhibition of TrkA signaling significantly reduced activation of ERK(1/2) in response to eotaxin-1."
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"Erk is activated by TrkA phosphorylation and turns on nuclear effectors involved in gene transcription."
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"Importantly, proNGF activates TrkA tyrosine phosphorylation, induces Erk and Akt activation, and causes PC12 cell differentiation."
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"Reduction of either GIPC1 or APPL1 decreased signaling by the TrkA receptor to MEK, ERK and Akt."
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"For example, activation of EGFR by EGF binding leads to transient ERK activation and proliferation of PC12 cells; whereas NGF activation of Trk triggers sustained ERK activation and PC12 differentiation."
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"TrkA-mediated activation of Erks and PLC−γ1 and p75NTR-mediated c-jun activation have been proposed to contribute to the pronounced pain observed upon NGF administration, via the opening of TRPV1 channels [5], [10], [11]."
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"These results suggest that NTRAP is required for TrkA to activate ERK1/2 in endosomes."
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"For example, p45 ICD is able to interact with the intracellular domain of the TrkA receptor and regulate TrkA mediated Erk1/2 activation XREF_BIBR."
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"On the whole data reported in XREF_FIG suggest that in PC12 cells ERKs activation, induced by stimulated TrkA receptor and TRK oncogenes, is responsible for STAT3 S727 but not Y705 phosphorylation."
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"To investigate whether trkA activates the Erk1/2 signaling pathway during responses to NGF, cells were incubated 60 min with the Erk1/2‐specific inhibitor, PD‐98059 (30 μmol/L, apical and basolateral; 9900L, Cell Signaling, Danvers, MA) or DMSO (0.06%)."
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"The proto-oncogene NTRK1 (also known as TRK) encodes a trans-membrane tyrosine kinase receptor for nerve growth factor and activates ERK, PI3K and phospholipase gamma (PLCgamma) signalling pathways."
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"Neuronal survival is maximally regulated by TrkA receptors localized at the PM via prolonged activation of the Akt signaling pathway, whereas neuronal differentiation is stimulated by sustained Erk activation by catalytically active TrkA in endosomes ( xref )."
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"Stimulation of neuronal TrkA with NGF has been shown to activate the MAPK components ERK1/2 and p38 MAPK XREF_BIBR."
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"Furthermore, they demonstrated in vitro that TRKA overexpression promoted proliferation, migration, and invasion, and that PI3K-Akt and ERK and MAPK pathways were activated by TRKA to promote this aggressive phenotype."
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"The p75 receptor signals mainly through stress associated pathways such as JNK, p53, and NF-kappaB, while Trk receptors activate the Akt and mitogen activated protein kinase and extracellular regulated kinase (MAPK and ERK) pathways."
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