PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 30672370-7 2019 Treatment with bpV increased extracellular signal-related kinase (Erk) activity after scratch injury in vitro, and rapamycin reduced influence by bpV on Erk phosphorylation. Sirolimus 115-124 mitogen-activated protein kinase 1 Homo sapiens 153-156 32736702-3 2020 In the present study, using cultured ARPE-19 cells, we determined that TGF-beta initiates a signaling pathway through extracellular signal-regulated kinase (ERK)-mammalian target of rapamycin complex 1 (mTORC1) that stimulates trans-differentiation and fibrosis of retinal pigment epithelium. Sirolimus 182-191 mitogen-activated protein kinase 1 Homo sapiens 118-155 32736702-3 2020 In the present study, using cultured ARPE-19 cells, we determined that TGF-beta initiates a signaling pathway through extracellular signal-regulated kinase (ERK)-mammalian target of rapamycin complex 1 (mTORC1) that stimulates trans-differentiation and fibrosis of retinal pigment epithelium. Sirolimus 182-191 mitogen-activated protein kinase 1 Homo sapiens 157-160 32104716-0 2020 Chloroquine and Rapamycin Augment Interleukin-37 Expression via the LC3, ERK, and AP-1 Axis in the Presence of Lipopolysaccharides. Sirolimus 16-25 mitogen-activated protein kinase 1 Homo sapiens 73-76 31358596-12 2019 Mycophenolate and rapamycin also down-regulated mTOR and extracellular signal-regulated kinase (ERK) phosphorylation and inhibited fibrotic responses in mesangial cells that were induced by anti-dsDNA antibodies or TGF-beta1. Sirolimus 18-27 mitogen-activated protein kinase 1 Homo sapiens 57-94 31358596-12 2019 Mycophenolate and rapamycin also down-regulated mTOR and extracellular signal-regulated kinase (ERK) phosphorylation and inhibited fibrotic responses in mesangial cells that were induced by anti-dsDNA antibodies or TGF-beta1. Sirolimus 18-27 mitogen-activated protein kinase 1 Homo sapiens 96-99 27616194-10 2016 Finally, we found that the extracellular signal-regulated kinase 1/2 (ERK1/2) signal was regulated by p53 whose expression was induced by rapamycin. Sirolimus 138-147 mitogen-activated protein kinase 1 Homo sapiens 27-68 28963126-7 2017 Rapamycin decreased basal and EGF stimulated HIF-1alpha and enhanced MAPK (ERK1/2) activation, while MAPK (ERK/12) inhibition downregulated HIF-1alpha expression and the phosphorylation of p70S6K. Sirolimus 0-9 mitogen-activated protein kinase 1 Homo sapiens 75-78 28734155-7 2017 In addition, rapamycin could also decrease the phosphorylation of p38, ERK1/2 and NF-kappaB p65 stimulated by anti-beta2GPI/beta2GPI or APS-IgG/beta2GPI complex, but it had no effect on JNK. Sirolimus 13-22 mitogen-activated protein kinase 1 Homo sapiens 66-69 31315300-10 2019 The Western blot results showed that the expression levels of Beclin1, LC3-I/II, and ERK were significantly elevated in HEMA-treated cells and in cells co-treated with rapamycin, an autophagic promoter. Sirolimus 168-177 mitogen-activated protein kinase 1 Homo sapiens 85-88 29475988-8 2018 Importantly, suppression of mTORC2 for 24 h with rapamycin or everolimus or treatment with mTOR active-site inhibitors enhanced HLA-II Ab-stimulated phosphorylation of ERK. Sirolimus 49-58 mitogen-activated protein kinase 1 Homo sapiens 168-171 27399332-3 2017 Here we show that Rheb-Y35N causes not only constitutive mTORC1 activation, but sustained activation of the MEK-ERK pathway in a TSC1/TSC2/TBC1D7 protein complex and mTORC1-independent manner, contributing to intrinsic resistance to rapamycin. Sirolimus 233-242 mitogen-activated protein kinase 1 Homo sapiens 112-115 26337526-9 2015 It was concluded that rapamycin suppresses TLR2-induced inflammatory responses by down-regulation of Erk and NF-kappaB signaling. Sirolimus 22-31 mitogen-activated protein kinase 1 Homo sapiens 101-104 22057915-1 2012 Inhibition of mTOR signaling by rapamycin has been shown to activate extracellular signal-regulated kinase 1 or 2 (ERK1/2) and Akt in various types of cancer cells, which contributes to rapamycin resistance. Sirolimus 32-41 mitogen-activated protein kinase 1 Homo sapiens 69-113 25758096-6 2015 In U937 cells, rapamycin alone increased the activity of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and the addition of ATO decreased the level of phosphorylated ERK, Ser473 phosphorylated Akt and anti-apoptotic Mcl-1 protein. Sirolimus 15-24 mitogen-activated protein kinase 1 Homo sapiens 129-133 25758096-6 2015 In U937 cells, rapamycin alone increased the activity of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and the addition of ATO decreased the level of phosphorylated ERK, Ser473 phosphorylated Akt and anti-apoptotic Mcl-1 protein. Sirolimus 15-24 mitogen-activated protein kinase 1 Homo sapiens 134-137 25116684-0 2014 Rapamycin-Induced apoptosis in HGF-stimulated lens epithelial cells by AKT/mTOR, ERK and JAK2/STAT3 pathways. Sirolimus 0-9 mitogen-activated protein kinase 1 Homo sapiens 81-84 25116684-6 2014 Further investigation of the underlying mechanism using siRNA transfection revealed that rapamycin could promote apoptosis of LECs via inhibiting HGF-induced phosphorylation of AKT/mTOR, ERK and JAK2/STAT3 signaling molecules. Sirolimus 89-98 mitogen-activated protein kinase 1 Homo sapiens 187-190 25116684-7 2014 Moreover, the forced expression of AKT, ERK and STAT3 could induce a significant suppression of apoptosis in these cells after treatment of rapamycin. Sirolimus 140-149 mitogen-activated protein kinase 1 Homo sapiens 40-43 25116684-8 2014 Together, these findings suggested that rapamycin-induced apoptosis in HGF-stimulated LECs is accompanied by inhibition of AKT/mTOR, ERK and JAK2/STAT3 pathways, which supports its use to inhibit PCO in preclinical studies and provides theoretical foundation for future possible practice. Sirolimus 40-49 mitogen-activated protein kinase 1 Homo sapiens 133-136 23580233-9 2013 Moreover, the effect of Mono-Pt involved the AKT1-MTOR-RPS6KB1 pathway and MAPK1 (ERK2)/MAPK3 (ERK1) signaling, since the MTOR inhibitor rapamycin increased, while the MAPK1/3 inhibitor U0126 decreased Mono-Pt-induced autophagic cell death. Sirolimus 137-146 mitogen-activated protein kinase 1 Homo sapiens 168-173 23607966-5 2013 The clinically available adenosine monophosphate-activated protein kinase activator, metformin, which is an antidiabetic drug, prevents rapamycin-induced ERK activation and the development of mechanical hypersensitivity and spontaneous pain. Sirolimus 136-145 mitogen-activated protein kinase 1 Homo sapiens 154-157 23426956-10 2013 Rosuvastatin alone did not alter phosphorylation of S6 and extracellular signal-regulated kinase (ERK), and at the higher concentration, rosuvastatin and rapamycin slightly decreased ERK phosphorylation. Sirolimus 154-163 mitogen-activated protein kinase 1 Homo sapiens 183-186 22552366-3 2012 In search of effective combination therapies, we show here that simultaneous targeting of EGFR with its inhibitor, erlotinib and mTOR with its inhibitor, rapamycin inhibits the phosphorylation and activation of downstream phosphatidylinositol 3-kinase (PI3K), Akt, mTOR and extracellular-signal-regulated kinase 1/2 (Erk1/2) pathways, resulting in the inhibition of cell cycle progression and the growth of both KRAS wild-type and mutated colorectal carcinoma cells. Sirolimus 178-187 mitogen-activated protein kinase 1 Homo sapiens 322-363 24676456-4 2014 Rapamycin-induced apoptosis was enhanced following the inhibition of the MEK/ERK pathway. Sirolimus 0-9 mitogen-activated protein kinase 1 Homo sapiens 77-80 24676456-10 2014 The present study demonstrates that rapamycin induces autophagy in Nara-H cells by activating the MEK/ERK signaling pathway, and the rapamycin-induced apoptosis can be enhanced by the MEK inhibitor, U0126. Sirolimus 36-45 mitogen-activated protein kinase 1 Homo sapiens 102-105 23741975-0 2014 Rapamycin interacts synergistically with idarubicin to induce T-leukemia cell apoptosis in vitro and in a mesenchymal stem cell simulated drug-resistant microenvironment via Akt/mammalian target of rapamycin and extracellular signal-related kinase signaling pathways. Sirolimus 0-9 mitogen-activated protein kinase 1 Homo sapiens 212-247 23741975-4 2014 Combined treatment with rapamycin and IDA down-regulated Bcl-2 and Mcl-1, and inhibited the activation of phosphoinositide 3-kinase (PI3K)/mTOR and extracellular signal-related kinase (ERK). Sirolimus 24-33 mitogen-activated protein kinase 1 Homo sapiens 148-183 23741975-4 2014 Combined treatment with rapamycin and IDA down-regulated Bcl-2 and Mcl-1, and inhibited the activation of phosphoinositide 3-kinase (PI3K)/mTOR and extracellular signal-related kinase (ERK). Sirolimus 24-33 mitogen-activated protein kinase 1 Homo sapiens 185-188 23403511-5 2013 Under normoxia, we found that rapamycin (100 nM) induced an increase of pCREB that was prevented by mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126 or cAMP-dependent protein kinase (PKA) inhibitor H89. Sirolimus 30-39 mitogen-activated protein kinase 1 Homo sapiens 178-181 23403511-10 2013 Our study demonstrated that rapamycin might be less effective in treating OSA cells under normoxia and provided the rationale for a combination of rapamycin and MEK/ERK inhibitor in the treatment of OSA. Sirolimus 28-37 mitogen-activated protein kinase 1 Homo sapiens 165-168 22617154-8 2012 Furthermore, the antiviral activity of TLR2 ligands was abolished by pretreatment with U0126 and rapamycin, inhibitors of the MAPK/ERK and PI3K/Akt pathways, respectively. Sirolimus 97-106 mitogen-activated protein kinase 1 Homo sapiens 126-130 22617154-8 2012 Furthermore, the antiviral activity of TLR2 ligands was abolished by pretreatment with U0126 and rapamycin, inhibitors of the MAPK/ERK and PI3K/Akt pathways, respectively. Sirolimus 97-106 mitogen-activated protein kinase 1 Homo sapiens 131-134 22057915-1 2012 Inhibition of mTOR signaling by rapamycin has been shown to activate extracellular signal-regulated kinase 1 or 2 (ERK1/2) and Akt in various types of cancer cells, which contributes to rapamycin resistance. Sirolimus 186-195 mitogen-activated protein kinase 1 Homo sapiens 69-113 21168265-1 2011 The anti-tumor activity of rapamycin is compromised by the feedback-loop-relevant hyperactive PI3K and ERK-MAPK pathway signaling. Sirolimus 27-36 mitogen-activated protein kinase 1 Homo sapiens 103-106 20512842-0 2010 Rapamycin regulates Akt and ERK phosphorylation through mTORC1 and mTORC2 signaling pathways. Sirolimus 0-9 mitogen-activated protein kinase 1 Homo sapiens 28-31 21168265-1 2011 The anti-tumor activity of rapamycin is compromised by the feedback-loop-relevant hyperactive PI3K and ERK-MAPK pathway signaling. Sirolimus 27-36 mitogen-activated protein kinase 1 Homo sapiens 107-111 19856312-0 2010 Rapamycin enhances chemotherapy-induced cytotoxicity by inhibiting the expressions of TS and ERK in gastric cancer cells. Sirolimus 0-9 mitogen-activated protein kinase 1 Homo sapiens 93-96 20512842-2 2010 In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin-mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors. Sirolimus 72-81 mitogen-activated protein kinase 1 Homo sapiens 99-102 20512842-2 2010 In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin-mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors. Sirolimus 72-81 mitogen-activated protein kinase 1 Homo sapiens 202-205 19139116-6 2009 Because extracellular signal-regulated kinase (ERK)/p38 activity facilitates IRES-mediated translation of some transcripts, we investigated ERK/p38 as regulators of AKT-dependent effects on rapamycin sensitivity. Sirolimus 190-199 mitogen-activated protein kinase 1 Homo sapiens 47-50 20512842-4 2010 We found that low concentrations rapamycin increased Akt and ERK phosphorylation through a mTORC1-dependent mechanism because knockdowned raptor induced the activation of Akt and ERK, but higher doses of rapamycin inhibited Akt and ERK phosphorylation mainly via the mTORC2 signaling pathway because that the silencing of rictor led to the inhibition of Akt and ERK phosphorylation. Sirolimus 33-42 mitogen-activated protein kinase 1 Homo sapiens 61-64 20512842-4 2010 We found that low concentrations rapamycin increased Akt and ERK phosphorylation through a mTORC1-dependent mechanism because knockdowned raptor induced the activation of Akt and ERK, but higher doses of rapamycin inhibited Akt and ERK phosphorylation mainly via the mTORC2 signaling pathway because that the silencing of rictor led to the inhibition of Akt and ERK phosphorylation. Sirolimus 33-42 mitogen-activated protein kinase 1 Homo sapiens 179-182 20512842-4 2010 We found that low concentrations rapamycin increased Akt and ERK phosphorylation through a mTORC1-dependent mechanism because knockdowned raptor induced the activation of Akt and ERK, but higher doses of rapamycin inhibited Akt and ERK phosphorylation mainly via the mTORC2 signaling pathway because that the silencing of rictor led to the inhibition of Akt and ERK phosphorylation. Sirolimus 33-42 mitogen-activated protein kinase 1 Homo sapiens 179-182 20512842-4 2010 We found that low concentrations rapamycin increased Akt and ERK phosphorylation through a mTORC1-dependent mechanism because knockdowned raptor induced the activation of Akt and ERK, but higher doses of rapamycin inhibited Akt and ERK phosphorylation mainly via the mTORC2 signaling pathway because that the silencing of rictor led to the inhibition of Akt and ERK phosphorylation. Sirolimus 33-42 mitogen-activated protein kinase 1 Homo sapiens 179-182 20512842-6 2010 Therefore, we combined PI3K and ERK inhibitors prevent rapamycin-induced Akt activation and enhanced antitumor effects of rapamycin. Sirolimus 55-64 mitogen-activated protein kinase 1 Homo sapiens 32-35 20512842-6 2010 Therefore, we combined PI3K and ERK inhibitors prevent rapamycin-induced Akt activation and enhanced antitumor effects of rapamycin. Sirolimus 122-131 mitogen-activated protein kinase 1 Homo sapiens 32-35 20512842-7 2010 Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin-mediated phosphorylation of Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin-based therapeutic approaches in cancer cells. Sirolimus 86-95 mitogen-activated protein kinase 1 Homo sapiens 132-135 20512842-7 2010 Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin-mediated phosphorylation of Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin-based therapeutic approaches in cancer cells. Sirolimus 86-95 mitogen-activated protein kinase 1 Homo sapiens 161-164 19539245-7 2009 When compared with monotherapy, combinatorial application of rapamycin and PD98059 had greater inhibitory effects on Tsc2 deficient cell proliferation, suggesting that combined suppression of mTOR and ERK/MAPK signaling pathways may have advantages over single mTOR inhibition in the treatment of TSC patients. Sirolimus 61-70 mitogen-activated protein kinase 1 Homo sapiens 201-204 19139116-6 2009 Because extracellular signal-regulated kinase (ERK)/p38 activity facilitates IRES-mediated translation of some transcripts, we investigated ERK/p38 as regulators of AKT-dependent effects on rapamycin sensitivity. Sirolimus 190-199 mitogen-activated protein kinase 1 Homo sapiens 140-143 19139116-9 2009 Furthermore, the ERK inhibitor successfully sensitized myeloma cells to rapamycin in terms of down-regulated D-cyclin protein expression and G1 arrest. Sirolimus 72-81 mitogen-activated protein kinase 1 Homo sapiens 17-20 18981735-7 2008 The combination of rapamycin with the MEK inhibitor U0126 significantly enhanced growth inhibitory effects of cancer cells, suggesting that MEK/ERK activation may counteract mTOR inhibitors" anticancer efficacy. Sirolimus 19-28 mitogen-activated protein kinase 1 Homo sapiens 144-147 18958173-11 2008 Although rapamycin efficiently inhibited S6 phosphorylation, it was less efficient than anti-EGFR antibody in reverting HMB45 reactivity and blocking ERK phosphorylation. Sirolimus 9-18 mitogen-activated protein kinase 1 Homo sapiens 150-153 18981735-9 2008 Moreover, the presence of erlotinib suppressed rapamycin-induced phosphorylation of Akt, ERK and eIF4E as well, implying that erlotinib can suppress mTOR inhibition-induced feedback activation of several survival signaling pathways including Akt, ERK and eIF4E. Sirolimus 47-56 mitogen-activated protein kinase 1 Homo sapiens 89-92 18981735-9 2008 Moreover, the presence of erlotinib suppressed rapamycin-induced phosphorylation of Akt, ERK and eIF4E as well, implying that erlotinib can suppress mTOR inhibition-induced feedback activation of several survival signaling pathways including Akt, ERK and eIF4E. Sirolimus 47-56 mitogen-activated protein kinase 1 Homo sapiens 247-250 18715846-1 2008 Preclinical studies using human gastric adenocarcinoma (GAC) cell lines have shown that the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, can inhibit tumor growth and that the extracellular signal-regulated kinase (ERK) of the Ras/Raf kinase/ERK pathway is related to chemoresistance and apoptosis. Sirolimus 112-121 mitogen-activated protein kinase 1 Homo sapiens 189-226 18312854-5 2008 We corroborated these results demonstrating that long-term exposure to rapamycin also inhibited ERK pathway activation in response to MHC class I signaling. Sirolimus 71-80 mitogen-activated protein kinase 1 Homo sapiens 96-99 10048588-5 1999 Selective inhibition of ERK, PI 3-kinase, and p70 S6 kinase with the inhibitors PD098059, LY294002, and rapamycin, respectively, inhibited VEGF-stimulated HUVEC proliferation. Sirolimus 104-113 mitogen-activated protein kinase 1 Homo sapiens 24-27 16959214-5 2006 It would seem that this increase in VEGFR-3 occurred via the ERK and mTOR pathways, since their respective inhibitors U0126, LY294002 or rapamycin were responsible for a decrease of VEGFR-3. Sirolimus 137-146 mitogen-activated protein kinase 1 Homo sapiens 61-64 17041093-3 2006 In tissue culture, all three cell lines showed decreased phosphorylated S6 ribosomal protein and decreased phosphorylated extracellular signal-regulated kinase (ERK) following treatment with rapamycin and erlotinib, respectively. Sirolimus 191-200 mitogen-activated protein kinase 1 Homo sapiens 122-159 17041093-3 2006 In tissue culture, all three cell lines showed decreased phosphorylated S6 ribosomal protein and decreased phosphorylated extracellular signal-regulated kinase (ERK) following treatment with rapamycin and erlotinib, respectively. Sirolimus 191-200 mitogen-activated protein kinase 1 Homo sapiens 161-164 15634685-0 2005 Cyclin D1 and c-myc internal ribosome entry site (IRES)-dependent translation is regulated by AKT activity and enhanced by rapamycin through a p38 MAPK- and ERK-dependent pathway. Sirolimus 123-132 mitogen-activated protein kinase 1 Homo sapiens 143-160 15634685-6 2005 Furthermore, we show that cyclin D1 and c-myc IRES function is enhanced following exposure to rapamycin and requires both p38 MAPK and RAF/MEK/ERK signaling, as specific inhibitors of these pathways reduce IRES-mediated translation and protein levels under conditions of quiescent AKT activity. Sirolimus 94-103 mitogen-activated protein kinase 1 Homo sapiens 143-146 12543789-4 2003 Despite the blocking of Ras-Erk signaling by the addition of PD 98059 (a MEK1 inhibitor) or by the overexpression of dominant-negative RasN17, IGF-I completely prevented rapamycin-induced death. Sirolimus 170-179 mitogen-activated protein kinase 1 Homo sapiens 28-31 12543789-9 2003 Furthermore, IGF-I prevented rapamycin-induced apoptosis when the Ras-Erk1-Erk2 and PI3K-Akt pathways were blocked simultaneously. Sirolimus 29-38 mitogen-activated protein kinase 1 Homo sapiens 75-79 15767555-0 2005 Rapamycin and UCN-01 synergistically induce apoptosis in human leukemia cells through a process that is regulated by the Raf-1/MEK/ERK, Akt, and JNK signal transduction pathways. Sirolimus 0-9 mitogen-activated protein kinase 1 Homo sapiens 131-134 15696050-10 2005 Rapamycin prevented the phosphorylation of p70S6K at the Thr 389 site (which correlates with enzyme activity), reduced ERK1/2 phosphorylation, but had no effect on the Thr 421/Ser 424 site or on p38(MAPK) phosphorylation. Sirolimus 0-9 mitogen-activated protein kinase 1 Homo sapiens 195-198 34797524-12 2022 Accordingly, the in vivo and in vitro experiments revealed that the mTOR inhibitor rapamycin further increased cell mortality and exhibited enhanced antitumor effect on GBM cells when co-treated with the ERK inhibitor. Sirolimus 83-92 mitogen-activated protein kinase 1 Homo sapiens 204-207 34715309-9 2022 But rapamycin could reverse the increasing expression of p-JNK/JNK, p-ERK/ERK and the release of IL-6 induced by GFP-SNCA Exo. Sirolimus 4-13 mitogen-activated protein kinase 1 Homo sapiens 70-73 34715309-9 2022 But rapamycin could reverse the increasing expression of p-JNK/JNK, p-ERK/ERK and the release of IL-6 induced by GFP-SNCA Exo. Sirolimus 4-13 mitogen-activated protein kinase 1 Homo sapiens 74-77 35571122-9 2022 Both mycophenolic acid and rapamycin inhibited inflammatory and fibrotic processes induced by TGF-beta1 or IL-6 by downregulating mTOR and ERK phosphorylation. Sirolimus 27-36 mitogen-activated protein kinase 1 Homo sapiens 139-142 34421360-5 2021 Here, we found that activation of ERK pathway was responsible for rapamycin drug resistance in non-small-cell lung cancer (NSCLC) cells. Sirolimus 66-75 mitogen-activated protein kinase 1 Homo sapiens 34-37 34421360-6 2021 Accordingly, rapamycin-resistant NSCLC cells were more sensitive to ERK inhibitor (ERKi), trametinib, and in turn, trametinib-resistant NSCLC cells were also susceptible to rapamycin. Sirolimus 13-22 mitogen-activated protein kinase 1 Homo sapiens 68-71 34421360-9 2021 Mechanistically, rapamycin in combination with trametinib resulted in a greater decrease of phosphorylation of AKT, ERK, mTOR and 4EBP1. Sirolimus 17-26 mitogen-activated protein kinase 1 Homo sapiens 116-119 33748286-6 2021 Furthermore, rapamycin reduced urinary protein-induced NGAL and KIM-1 secretion and cell growth inhibition, while chloroquine played the opposite effect, indicating that autophagy activation by ERK pathway was an adaptive response in the exposure to urinary proteins. Sirolimus 13-22 mitogen-activated protein kinase 1 Homo sapiens 194-197