PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 23308050-0 2012 Valproic acid upregulates NKG2D ligand expression through an ERK-dependent mechanism and potentially enhances NK cell-mediated lysis of myeloma. Valproic Acid 0-13 mitogen-activated protein kinase 1 Homo sapiens 61-64 23308050-8 2012 These data indicate that increased sensitivity of VPA-treated myeloma cells to NK cell lysis is caused by higher NKG2D ligand expression, resulting from more active ERK signaling pathway. Valproic Acid 50-53 mitogen-activated protein kinase 1 Homo sapiens 165-168 17514356-3 2007 Beyond the enhancement of gamma-aminobutyric acid-mediated neurotransmission, valproate has been found to affect signalling systems like the Wnt/beta-catenin and ERK pathways and to interfere with inositol and arachidonate metabolism. Valproic Acid 78-87 mitogen-activated protein kinase 1 Homo sapiens 162-165 19419383-7 2009 This study investigates the possibility that the anticonvulsant valproate (VPA), which robustly activates the ERK mitogen-activated protein kinase (MAPK) cascade, may exert cytoprotective effects on VSMC through the Notch3/c-FLIP pathway. Valproic Acid 64-73 mitogen-activated protein kinase 1 Homo sapiens 110-113 19419383-7 2009 This study investigates the possibility that the anticonvulsant valproate (VPA), which robustly activates the ERK mitogen-activated protein kinase (MAPK) cascade, may exert cytoprotective effects on VSMC through the Notch3/c-FLIP pathway. Valproic Acid 64-73 mitogen-activated protein kinase 1 Homo sapiens 148-152 19419383-7 2009 This study investigates the possibility that the anticonvulsant valproate (VPA), which robustly activates the ERK mitogen-activated protein kinase (MAPK) cascade, may exert cytoprotective effects on VSMC through the Notch3/c-FLIP pathway. Valproic Acid 75-78 mitogen-activated protein kinase 1 Homo sapiens 110-113 19419383-7 2009 This study investigates the possibility that the anticonvulsant valproate (VPA), which robustly activates the ERK mitogen-activated protein kinase (MAPK) cascade, may exert cytoprotective effects on VSMC through the Notch3/c-FLIP pathway. Valproic Acid 75-78 mitogen-activated protein kinase 1 Homo sapiens 148-152 21055435-9 2011 ERK gene was upregulated in cortex and striatum by the acute treatment with valproate and with the combination of haloperidol or quetiapine plus valproate, whereas no significant differences were noticed in GSK3b expression among treatments. Valproic Acid 76-85 mitogen-activated protein kinase 1 Homo sapiens 0-3 21055435-9 2011 ERK gene was upregulated in cortex and striatum by the acute treatment with valproate and with the combination of haloperidol or quetiapine plus valproate, whereas no significant differences were noticed in GSK3b expression among treatments. Valproic Acid 145-154 mitogen-activated protein kinase 1 Homo sapiens 0-3 18677583-0 2009 Evidence for involvement of ERK, PI3K, and RSK in induction of Bcl-2 by valproate. Valproic Acid 72-81 mitogen-activated protein kinase 1 Homo sapiens 28-31 18677583-8 2009 These data collectively suggest that valproate induces Bcl-2 regulation partially through activations of the ERK and PI3K cascades and their convergent kinase, RSK, although other unknown mechanism(s) are likely involved. Valproic Acid 37-46 mitogen-activated protein kinase 1 Homo sapiens 109-112 17448293-4 2007 Focused studies uncovered the potential of valproic acid to interfere with multiple regulatory mechanisms including histone deacetylases, GSK3 alpha and beta, Akt, the ERK pathway, the phosphoinositol pathway, the tricarboxylic acid cycle, GABA, and the OXPHOS system. Valproic Acid 43-56 mitogen-activated protein kinase 1 Homo sapiens 168-171 16759735-2 2006 The bipolar disorder treatment, valproic acid (VPA), increases the activity of this pathway by modulating extracellular signal-regulated kinase 2 (ERK2) phosphorylation through an unknown mechanism. Valproic Acid 32-45 mitogen-activated protein kinase 1 Homo sapiens 147-151 16759735-2 2006 The bipolar disorder treatment, valproic acid (VPA), increases the activity of this pathway by modulating extracellular signal-regulated kinase 2 (ERK2) phosphorylation through an unknown mechanism. Valproic Acid 47-50 mitogen-activated protein kinase 1 Homo sapiens 147-151 16759735-4 2006 We find that, similar to mammalian systems, VPA causes a transient increase in the activation of the MAPK signalling pathway, as shown by ERK2 phosphorylation. Valproic Acid 44-47 mitogen-activated protein kinase 1 Homo sapiens 101-105 16759735-4 2006 We find that, similar to mammalian systems, VPA causes a transient increase in the activation of the MAPK signalling pathway, as shown by ERK2 phosphorylation. Valproic Acid 44-47 mitogen-activated protein kinase 1 Homo sapiens 138-142 16123451-9 2005 The mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 inhibited VPA-induced Erk 1/2 phosphorylation but did not affect VPA-induced increased HCMV replication. Valproic Acid 78-81 mitogen-activated protein kinase 1 Homo sapiens 90-97 16739251-6 2006 Furthermore, activation of the ERK pathway was involved in VPA-mediated CD61/CD41 expression and in cell adhesion, as demonstrated by using the MEK/ERK inhibitor U0126. Valproic Acid 59-62 mitogen-activated protein kinase 1 Homo sapiens 31-34 16739251-6 2006 Furthermore, activation of the ERK pathway was involved in VPA-mediated CD61/CD41 expression and in cell adhesion, as demonstrated by using the MEK/ERK inhibitor U0126. Valproic Acid 59-62 mitogen-activated protein kinase 1 Homo sapiens 148-151 16167071-0 2006 Valproic acid induces extracellular signal-regulated kinase 1/2 activation and inhibits apoptosis in endothelial cells. Valproic Acid 0-13 mitogen-activated protein kinase 1 Homo sapiens 22-63 12720479-4 2003 Lithium and valproate also robustly activate a signaling cascade utilized by endogenous growth factors-the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway. Valproic Acid 12-21 mitogen-activated protein kinase 1 Homo sapiens 107-144 15269271-0 2004 Mood stabilizer valproate promotes ERK pathway-dependent cortical neuronal growth and neurogenesis. Valproic Acid 16-25 mitogen-activated protein kinase 1 Homo sapiens 35-38 15269271-10 2004 Similar to neurotrophic factors, valproate enhanced ERK pathway-dependent cortical neuronal growth. Valproic Acid 33-42 mitogen-activated protein kinase 1 Homo sapiens 52-55 15269271-13 2004 Together, these data demonstrate that valproate activates the ERK pathway and induces ERK pathway-mediated neurotrophic actions. Valproic Acid 38-47 mitogen-activated protein kinase 1 Homo sapiens 62-65 15269271-13 2004 Together, these data demonstrate that valproate activates the ERK pathway and induces ERK pathway-mediated neurotrophic actions. Valproic Acid 38-47 mitogen-activated protein kinase 1 Homo sapiens 86-89 15654930-7 2005 Moreover, other activators of ERK/MAPK, such as epidermal growth factor and phorbol 12-myristate 13-acetate, mimic the neurotrophic effects of VPA. Valproic Acid 143-146 mitogen-activated protein kinase 1 Homo sapiens 30-33 15654930-7 2005 Moreover, other activators of ERK/MAPK, such as epidermal growth factor and phorbol 12-myristate 13-acetate, mimic the neurotrophic effects of VPA. Valproic Acid 143-146 mitogen-activated protein kinase 1 Homo sapiens 34-38 15654930-9 2005 In contrast, both lithium and VPA activate ERK/MAPK in rat primary cortical neurons. Valproic Acid 30-33 mitogen-activated protein kinase 1 Homo sapiens 47-51 12720479-4 2003 Lithium and valproate also robustly activate a signaling cascade utilized by endogenous growth factors-the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway. Valproic Acid 12-21 mitogen-activated protein kinase 1 Homo sapiens 146-149 28421199-0 2017 Valproic Acid Protects Primary Dopamine Neurons from MPP+-Induced Neurotoxicity: Involvement of GSK3beta Phosphorylation by Akt and ERK through the Mitochondrial Intrinsic Apoptotic Pathway. Valproic Acid 0-13 mitogen-activated protein kinase 1 Homo sapiens 132-135 12221674-3 2002 Investigation of the role of the mitogen-activated protein kinase (MAPK) pathways by Western blot analysis and use of specific kinase inhibitors suggests that inhibition of ERK pathway and activation of the p38 pathway may contribute to the HbF-inducing activity of valproate. Valproic Acid 266-275 mitogen-activated protein kinase 1 Homo sapiens 67-71 12221674-3 2002 Investigation of the role of the mitogen-activated protein kinase (MAPK) pathways by Western blot analysis and use of specific kinase inhibitors suggests that inhibition of ERK pathway and activation of the p38 pathway may contribute to the HbF-inducing activity of valproate. Valproic Acid 266-275 mitogen-activated protein kinase 1 Homo sapiens 173-176 35078573-9 2022 Conclusion VPA up-regulates the expression of MICA and MICB in melanoma cells and enhances the killing effect of NK92 cells on melanoma, which may be related to the activation of MEK/ERK signaling pathway. Valproic Acid 11-14 mitogen-activated protein kinase 1 Homo sapiens 183-186 28421199-3 2017 VPA reversed MPP+-induced mitochondrial apoptosis and counteracted MPP+-induced extracellular signal-regulated kinase (ERK) and Akt repression and inhibited glycogen synthase kinase 3beta (GSK3beta) activation through induction of GSK3beta phosphorylation. Valproic Acid 0-3 mitogen-activated protein kinase 1 Homo sapiens 80-117 28421199-3 2017 VPA reversed MPP+-induced mitochondrial apoptosis and counteracted MPP+-induced extracellular signal-regulated kinase (ERK) and Akt repression and inhibited glycogen synthase kinase 3beta (GSK3beta) activation through induction of GSK3beta phosphorylation. Valproic Acid 0-3 mitogen-activated protein kinase 1 Homo sapiens 119-122 28421199-4 2017 Moreover, inhibitors of the PI3K and MAPK pathways abolished GSK3beta phosphorylation and diminished the VPA-induced neuroprotective effect. Valproic Acid 105-108 mitogen-activated protein kinase 1 Homo sapiens 37-41 11418608-3 2001 VPA-induced activation of ERK was blocked by the mitogen-activated protein kinase/ERK kinase inhibitor PD098059 and dominant-negative Ras and Raf mutants but not by dominant-negative stress-activated protein kinase/ERK kinase and mitogen-activated protein kinase kinase 6 mutants. Valproic Acid 0-3 mitogen-activated protein kinase 1 Homo sapiens 26-29 11418608-3 2001 VPA-induced activation of ERK was blocked by the mitogen-activated protein kinase/ERK kinase inhibitor PD098059 and dominant-negative Ras and Raf mutants but not by dominant-negative stress-activated protein kinase/ERK kinase and mitogen-activated protein kinase kinase 6 mutants. Valproic Acid 0-3 mitogen-activated protein kinase 1 Homo sapiens 82-85 11418608-3 2001 VPA-induced activation of ERK was blocked by the mitogen-activated protein kinase/ERK kinase inhibitor PD098059 and dominant-negative Ras and Raf mutants but not by dominant-negative stress-activated protein kinase/ERK kinase and mitogen-activated protein kinase kinase 6 mutants. Valproic Acid 0-3 mitogen-activated protein kinase 1 Homo sapiens 82-85 35078573-0 2022 (Valproate up-regulates the expression of NKG2DL through the MEK/ERK signaling pathway to enhance the killing effect of NK cells on A375 human melanoma cells). Valproic Acid 1-10 mitogen-activated protein kinase 1 Homo sapiens 65-68 35078573-1 2022 Objective To investigate the effect of sodium valproate (VPA) on the expression of NKG2D ligand and the killing effect of NK cells on melanoma cells through MEK/ERK signaling pathway. Valproic Acid 39-55 mitogen-activated protein kinase 1 Homo sapiens 161-164 35078573-1 2022 Objective To investigate the effect of sodium valproate (VPA) on the expression of NKG2D ligand and the killing effect of NK cells on melanoma cells through MEK/ERK signaling pathway. Valproic Acid 57-60 mitogen-activated protein kinase 1 Homo sapiens 161-164 35078573-3 2022 In the group with A375 cells treated with the MEK/ERK signaling pathway inhibitor PD98059 combined with VPA, the protein expressions of MICA and MICB were detected by Western blotting, the expressions of MICA and MICB were detected by flow cytometry, and the killing effect of NK92 cells on A375 cells was detected by LDH release assay. Valproic Acid 104-107 mitogen-activated protein kinase 1 Homo sapiens 50-53 24472423-5 2014 In addition, we found that VPA is able to increase these endodermal genes in hUCMSCs by activating signal transduction of AKT and ERK. Valproic Acid 27-30 mitogen-activated protein kinase 1 Homo sapiens 130-133 25581256-4 2015 These signals are inhibited in neuronal cells that express constitutively activated MEK/ERK and/or PI3-K/Akt survival pathways, allowing them to resist VPA-induced cell death. Valproic Acid 152-155 mitogen-activated protein kinase 1 Homo sapiens 88-91 27802437-0 2016 Valproic Acid Promotes Human Glioma U87 Cells Apoptosis and Inhibits Glycogen Synthase Kinase-3beta Through ERK/Akt Signaling. Valproic Acid 0-13 mitogen-activated protein kinase 1 Homo sapiens 108-111 27802437-5 2016 However, the MAPK inhibitor PD98059 and/or PI3K inhibitor LY294002 were able to antagonize the effects of VPA by abolishing ERK/Akt activations and cancelling GSK3beta suppression, thus it impaired VPA apoptosis-inducing effects on glioma cells. Valproic Acid 106-109 mitogen-activated protein kinase 1 Homo sapiens 13-17 27802437-5 2016 However, the MAPK inhibitor PD98059 and/or PI3K inhibitor LY294002 were able to antagonize the effects of VPA by abolishing ERK/Akt activations and cancelling GSK3beta suppression, thus it impaired VPA apoptosis-inducing effects on glioma cells. Valproic Acid 106-109 mitogen-activated protein kinase 1 Homo sapiens 124-127 24472423-7 2014 The effects of VPA on modulating hUCMSCs fate were diminished by blocking AKT and ERK activation using specific signaling inhibitors. Valproic Acid 15-18 mitogen-activated protein kinase 1 Homo sapiens 82-85 24472423-8 2014 Together, our results suggest that VPA contributes to the lineage conversion of hUCMSCs to hepatic cell fate by upregulating the expression of endodermal genes through AKT and ERK activation. Valproic Acid 35-38 mitogen-activated protein kinase 1 Homo sapiens 176-179 24817927-7 2014 When TGF-beta-sensitized cells were treated with sorafenib plus VPA, the levels of phosphorylated ERK and AKT were considerably suppressed and the numbers of dead cells were increased by 3.7-5.7-fold compared with those exposed to sorafenib alone (P<0.05). Valproic Acid 64-67 mitogen-activated protein kinase 1 Homo sapiens 98-101 23073524-0 2014 Valproate activates ERK signaling pathway in primary human hepatocytes. Valproic Acid 0-9 mitogen-activated protein kinase 1 Homo sapiens 20-23 23073524-3 2014 METHODS: In the present study, we examined the effect of VPA on the extracellular signal-related kinase (ERK, p42/p44) pathway (Ras-Raf-MEK-ERK) belonging to the mitogen-activated protein kinases (MAPKs) pathways in primary human hepatocytes. Valproic Acid 57-60 mitogen-activated protein kinase 1 Homo sapiens 68-103 23073524-3 2014 METHODS: In the present study, we examined the effect of VPA on the extracellular signal-related kinase (ERK, p42/p44) pathway (Ras-Raf-MEK-ERK) belonging to the mitogen-activated protein kinases (MAPKs) pathways in primary human hepatocytes. Valproic Acid 57-60 mitogen-activated protein kinase 1 Homo sapiens 105-108 23073524-3 2014 METHODS: In the present study, we examined the effect of VPA on the extracellular signal-related kinase (ERK, p42/p44) pathway (Ras-Raf-MEK-ERK) belonging to the mitogen-activated protein kinases (MAPKs) pathways in primary human hepatocytes. Valproic Acid 57-60 mitogen-activated protein kinase 1 Homo sapiens 140-143 23073524-5 2014 RESULTS: We found that VPA in a therapeutically relevant concentration (500 microM) activates the ERK pathway, as indicated by increased ERK Thr202/Tyr204 phosphorylation. Valproic Acid 23-26 mitogen-activated protein kinase 1 Homo sapiens 98-101 23073524-5 2014 RESULTS: We found that VPA in a therapeutically relevant concentration (500 microM) activates the ERK pathway, as indicated by increased ERK Thr202/Tyr204 phosphorylation. Valproic Acid 23-26 mitogen-activated protein kinase 1 Homo sapiens 137-140 23073524-9 2014 CONCLUSION: We conclude that VPA activates the ERK pathway in primary human hepatocytes. Valproic Acid 29-32 mitogen-activated protein kinase 1 Homo sapiens 47-50