PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 19135033-6 2009 In addition, we demonstrate that the RA-mediated activation of Galanin promoter activity and Brn-3a N-terminal transcriptional activity are both blocked by pan-MEK inhibitors, and show that the expression of a constitutively-active mutant of MEK1, but not MEK5, is sufficient to increase Brn-3a activity. Tretinoin 37-39 mitogen-activated protein kinase kinase 7 Homo sapiens 160-163 15474987-6 2005 Pharmacological studies using PD098059 (a MEK inhibitor), SB203580 (a p38 MAPK inhibitor) and SP600125 (a JNK inhibitor) suggested that the MEK pathway was important for VD3 and ATRA-induced differentiation and also its enhancement by MG or HK, the p38 MAPK pathway had a inhibitory effect and the JNK pathway had little influence. Tretinoin 178-182 mitogen-activated protein kinase kinase 7 Homo sapiens 140-143 18682553-2 2008 In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-trans retinoic acid (atRA) to stimulate complex formation of extracellular signal-regulated kinase 2 (ERK2) with its upstream kinase, mitogen-activated protein kinase kinase (MEK). Tretinoin 106-119 mitogen-activated protein kinase kinase 7 Homo sapiens 234-273 17646388-4 2007 We found that RA rapidly activates the protein kinase Calpha isozyme and transmits the activation signal to CREB via the Raf/MEK/extracellular signal-regulated kinase/p90 ribosomal S6 kinase (RSK) pathway. Tretinoin 14-16 mitogen-activated protein kinase kinase 7 Homo sapiens 125-128 18682553-2 2008 In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-trans retinoic acid (atRA) to stimulate complex formation of extracellular signal-regulated kinase 2 (ERK2) with its upstream kinase, mitogen-activated protein kinase kinase (MEK). Tretinoin 106-119 mitogen-activated protein kinase kinase 7 Homo sapiens 275-278 18682553-2 2008 In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-trans retinoic acid (atRA) to stimulate complex formation of extracellular signal-regulated kinase 2 (ERK2) with its upstream kinase, mitogen-activated protein kinase kinase (MEK). Tretinoin 121-125 mitogen-activated protein kinase kinase 7 Homo sapiens 234-273 18682553-2 2008 In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-trans retinoic acid (atRA) to stimulate complex formation of extracellular signal-regulated kinase 2 (ERK2) with its upstream kinase, mitogen-activated protein kinase kinase (MEK). Tretinoin 121-125 mitogen-activated protein kinase kinase 7 Homo sapiens 275-278 18082883-0 2008 Retinoid X receptor alpha is highly phosphorylated in retinoic acid-resistant HL-60R cells and the combination of 9-cis retinoic acid plus MEK inhibitor induces apoptosis in the cells. Tretinoin 54-67 mitogen-activated protein kinase kinase 7 Homo sapiens 139-142 18082883-3 2008 However, when the HL-60R cells were treated with the combination of 9-cis RA plus PD98059, MEK inhibitor, the p-RXR alpha and RXR alpha proteins all markedly decreased. Tretinoin 74-76 mitogen-activated protein kinase kinase 7 Homo sapiens 91-94 18064629-10 2008 We conclude that atRA protects against UV-induced down-regulation AQP3 and decrease in water permeability, reduction in cell migration and delayed in vitro wound healing via trans-activation of EGFR and inhibition on ROS-mediated MEK/ERK pathway. Tretinoin 17-21 mitogen-activated protein kinase kinase 7 Homo sapiens 230-233 18006504-2 2008 In this study, RA is found to cause MAPK activation with sustained association of RAF to MEK or ERK, leading to a MAPK-dependent accumulation of p21(Waf1/Cip1) and binding to CDK2 blocking G(1)/S transition. Tretinoin 15-17 mitogen-activated protein kinase kinase 7 Homo sapiens 89-92 11683493-0 2001 Retinoic acid causes MEK-dependent RAF phosphorylation through RARalpha plus RXR activation in HL-60 cells. Tretinoin 0-13 mitogen-activated protein kinase kinase 7 Homo sapiens 21-24 11683493-3 2001 This motivates the question of whether RA also activated RAF as part of a typical RAF/MEK/MAPK cascade. Tretinoin 39-41 mitogen-activated protein kinase kinase 7 Homo sapiens 86-89 11683493-1 2001 Retinoic acid (RA) is known to cause the myeloid differentiation of HL-60 human myeloblastic leukemia cells in a process requiring MEK-dependent ERK2 activation. Tretinoin 0-13 mitogen-activated protein kinase kinase 7 Homo sapiens 131-134 11683493-10 2001 RA-induced MEK-dependent RAF phosphorylation is not due to changes in the amount of cellular MEK. Tretinoin 0-2 mitogen-activated protein kinase kinase 7 Homo sapiens 11-14 11683493-13 2001 In summary, RA induces a MEK-dependent prolonged RAF activation, whose slow onset occurs after ERK2 activation but still well before cell cycle arrest and cell differentiation. Tretinoin 12-14 mitogen-activated protein kinase kinase 7 Homo sapiens 25-28 11683493-1 2001 Retinoic acid (RA) is known to cause the myeloid differentiation of HL-60 human myeloblastic leukemia cells in a process requiring MEK-dependent ERK2 activation. Tretinoin 15-17 mitogen-activated protein kinase kinase 7 Homo sapiens 131-134 10852350-14 2000 A significant unanticipated finding was that retinoic acid caused a MEK-dependent increase in the amount of phosphorylated RAF. Tretinoin 45-58 mitogen-activated protein kinase kinase 7 Homo sapiens 68-71 34731634-7 2021 In a proof-of-principle approach, we use these datasets to show that MEK signaling is required for M2-type polarization by promoting peroxisome proliferator-activated receptor-gamma (PPARgamma)-induced retinoic acid signaling. Tretinoin 202-215 mitogen-activated protein kinase kinase 7 Homo sapiens 69-72 34355652-2 2021 In the present study, a clinically achievable concentration of trametinib, a highly selective inhibitor of MEK, enhanced ATRA-induced differentiation in AML cell lines, HL-60 and U937 as well as AML primary cells. Tretinoin 121-125 mitogen-activated protein kinase kinase 7 Homo sapiens 107-110 10852350-1 2000 Retinoic acid is known to cause the myeloid differentiation and G1/0 cell cycle arrest of HL-60 cells in a process that requires mitogen-activated protein/extracellular signal regulated kinase (MEK)-dependent extracellular signal regulated kinase (ERK)2 activation. Tretinoin 0-13 mitogen-activated protein kinase kinase 7 Homo sapiens 194-197 10852350-11 2000 But PD98059 eliminated detectable ERK2 activation, as well as inhibited RAF phosphorylation, in untreated and retinoic acid-treated wild-type HL-60 and cFMS transfectants, consistent with MEK or ERK feedback-regulation of RAF, in all four cases. Tretinoin 110-123 mitogen-activated protein kinase kinase 7 Homo sapiens 188-191 10852350-12 2000 Since PD98059 blocks the cFMS-conferred enhancement of the retinoic acid-induced differentiation, but not growth arrest, the data indicate that cFMS-enhanced differentiation acts primarily through MEK and ERK2, but cFMS-enhanced G1/0 arrest allied with RB hypophosphorylation depends on another cFMS signal route, which by itself can effect G1/0 arrest without activated ERK2. Tretinoin 59-72 mitogen-activated protein kinase kinase 7 Homo sapiens 197-200 9679985-2 1998 ERK2 activation by mitogen-activated protein/ERK kinase (MEK) was necessary for RA-induced differentiation in studies using PD98059 to block MEK phosphorylation. Tretinoin 80-82 mitogen-activated protein kinase kinase 7 Homo sapiens 57-60 9679985-2 1998 ERK2 activation by mitogen-activated protein/ERK kinase (MEK) was necessary for RA-induced differentiation in studies using PD98059 to block MEK phosphorylation. Tretinoin 80-82 mitogen-activated protein kinase kinase 7 Homo sapiens 141-144 9679985-11 1998 The results thus show that RA augments MEK-dependent ERK2 activation that is needed for subsequent RB hypophosphorylation, cell differentiation, and G0 arrest. Tretinoin 27-29 mitogen-activated protein kinase kinase 7 Homo sapiens 39-42 32882760-8 2020 A RAF-1/MEK/ERK pathway was founded to be associated with AG-221 and ATRA-induced differentiation in IDH2-mutant AML cells. Tretinoin 69-73 mitogen-activated protein kinase kinase 7 Homo sapiens 8-11 32032659-3 2020 Roscovitine co-treatment enhanced ATRA-induced expression of pS259- pS289/296/301- pS621-c-Raf, pS217/221-Mek, Src Family Kinases (SFKs) Lyn and Fgr and SFK Y416 phosphorylation, adaptor proteins c-Cbl and Slp-76, Vav, and acetylated 14-3-3 in the signalsome. Tretinoin 34-38 mitogen-activated protein kinase kinase 7 Homo sapiens 106-109 32361568-7 2020 The MEK inhibitor also inhibited the differentiation of ATRA-HL cells to neutrophils. Tretinoin 56-60 mitogen-activated protein kinase kinase 7 Homo sapiens 4-7 30576481-9 2019 RA treatment elicited activation of the MEK-ERK pathway and induced rapid and transient activation of the extracellular signal-regulated kinase 1/2 (ERK-1/2). Tretinoin 0-2 mitogen-activated protein kinase kinase 7 Homo sapiens 40-43 29131833-0 2017 MEK inhibitors enhance therapeutic response towards ATRA in NF1 associated malignant peripheral nerve sheath tumors (MPNST) in-vitro. Tretinoin 52-56 mitogen-activated protein kinase kinase 7 Homo sapiens 0-3 31218101-5 2019 Therefore, RAF-1-independent MEK/ERK signaling was required for enz-ATRA treatment-induced differentiation via modulation of the protein levels of C/EBPbeta and/or PU.1. Tretinoin 68-72 mitogen-activated protein kinase kinase 7 Homo sapiens 29-32 23656719-12 2013 FICZ causes changes in signaling events that are known to drive differentiation, and notably augments the RA-induced sustained activation of the RAF/MEK/ERK axis of the mitogen-activated protein kinase (MAPK) cascade. Tretinoin 106-108 mitogen-activated protein kinase kinase 7 Homo sapiens 149-152 27665842-0 2016 Staurosporine enhances ATRA-induced granulocytic differentiation in human leukemia U937 cells via the MEK/ERK signaling pathway. Tretinoin 23-27 mitogen-activated protein kinase kinase 7 Homo sapiens 102-105 27665842-10 2016 Taken together, we concluded that staurosporine enhanced ATRA-induced granulocytic differentiation in U937 cells via MEK/ERK-mediated modulation of the protein level of C/EBPs. Tretinoin 57-61 mitogen-activated protein kinase kinase 7 Homo sapiens 117-120 27101150-0 2016 RAF-1/MEK/ERK pathway regulates ATRA-induced differentiation in acute promyelocytic leukemia cells through C/EBPbeta, C/EBPepsilon and PU.1. Tretinoin 32-36 mitogen-activated protein kinase kinase 7 Homo sapiens 6-9 27101150-2 2016 Recently, MEK/ERK cascade was reported to be involved in all-trans retinoic acid (ATRA) induced differentiation in acute promyelocytic leukemia (APL) cells. Tretinoin 67-80 mitogen-activated protein kinase kinase 7 Homo sapiens 10-13 27101150-2 2016 Recently, MEK/ERK cascade was reported to be involved in all-trans retinoic acid (ATRA) induced differentiation in acute promyelocytic leukemia (APL) cells. Tretinoin 82-86 mitogen-activated protein kinase kinase 7 Homo sapiens 10-13 27101150-5 2016 ATRA-enhanced protein levels of C/EBPbeta, C/EBPepsilon and PU.1, which were required for differentiation in APL cells, were suppressed by the specific inhibitor of MEK. Tretinoin 0-4 mitogen-activated protein kinase kinase 7 Homo sapiens 165-168 27101150-7 2016 Taken together, our study suggested that RAF-1/MEK/ERK cascade was involved in ATRA-induced differentiation in APL cells through enhancing the protein level of C/EBPbeta, C/EBPepsilon and PU.1. Tretinoin 79-83 mitogen-activated protein kinase kinase 7 Homo sapiens 47-50 27074819-0 2016 The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK/ERK mediated RARalpha/STAT1 axis. Tretinoin 75-88 mitogen-activated protein kinase kinase 7 Homo sapiens 135-138 24769642-4 2014 Taken together, we concluded that the combination of ATRA and staurosporine could overcome differentiation block via MEK/ERK signaling pathway in ATRA-resistant APL cell lines. Tretinoin 53-57 mitogen-activated protein kinase kinase 7 Homo sapiens 117-120 23404856-6 2013 We found that MEK inhibition decreased NIS protein levels in all-trans retinoic acid/hydrocortisone-treated MCF-7 cells as well as human breast cancer cells expressing exogenous NIS. Tretinoin 71-84 mitogen-activated protein kinase kinase 7 Homo sapiens 14-17 23396089-9 2013 In contrast, ATRA increased the expression of SOSC2, BRAF, MEK, and ERK genes. Tretinoin 13-17 mitogen-activated protein kinase kinase 7 Homo sapiens 59-62 23554907-3 2013 However, RA-treated RA-resistant HL60 continue to exhibit sustained MEK/ERK activation, and one of the two sequentially emergent resistant lines retains RA-inducible CD38 expression. Tretinoin 9-11 mitogen-activated protein kinase kinase 7 Homo sapiens 68-71 20615082-4 2010 ATO augmented ATRA-induced RAF/MEK/ERK axis signaling, expression of CD11b and p47(PHOX), and inducible oxidative metabolism. Tretinoin 14-18 mitogen-activated protein kinase kinase 7 Homo sapiens 31-34 20655465-7 2010 Inhibition of MEK signaling downstream of NF1 restores responsiveness to RA, suggesting a therapeutic strategy to overcome RA resistance in NF1-deficient neuroblastomas. Tretinoin 73-75 mitogen-activated protein kinase kinase 7 Homo sapiens 14-17 20655465-7 2010 Inhibition of MEK signaling downstream of NF1 restores responsiveness to RA, suggesting a therapeutic strategy to overcome RA resistance in NF1-deficient neuroblastomas. Tretinoin 123-125 mitogen-activated protein kinase kinase 7 Homo sapiens 14-17