{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMAPK1, which encodes one of the extracellular signal‐regulated kinases (ERK), is a central effector in many mitogen‐activated protein kinase (MAPK) cascades that regulate cell cycle progression, proliferation, differentiation, and even senescence. Studies have shown that in normal cells sustained MAPK1/ERK2 activity is required for G1‐to‐S phase progression through induction of positive cell‐cycle regulators, whereas hyperactivation (often downstream of oncogenic Ras) can trigger the accumulation of cyclin‐dependent kinase inhibitors and induce premature cell cycle arrest or senescence. In addition, ERK activity is critical for proper cytokinesis as well as for maintaining the balance between growth and stress responses through interactions with targets that control cell division and survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in cell‐cycle regulation, MAPK1/ERK2 functions downstream of numerous receptors – including G protein–coupled and tyrosine kinase receptors – to transduce extracellular signals via both rapid, G protein–dependent mechanisms as well as slower, β‐arrestin–mediated pathways. This receptor‐driven ERK activation modulates the activities of key enzymes such as sphingosine kinase 1, influences cytoskeletal reorganization during processes like cellular migration, wound healing, and cytokinesis, and plays an instrumental role in epithelial‐to‐mesenchymal transition by engaging specific docking motifs that allow selective phosphorylation of targets involved in cell motility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMAPK1/ERK2 also exerts a powerful influence on nuclear events. By phosphorylating transcription factors and nuclear shuttling proteins, ERK2 drives the transcriptional programs required for both physiological adaptations to stress and developmental decisions. In several contexts, phosphorylation events mediated by ERK2 facilitate its own nuclear accumulation by unveiling noncanonical nuclear translocation signals, ultimately leading to altered gene expression – from the regulation of growth factor–responsive genes and mucin synthesis to the modulation of interferon‐regulated promoters. These nuclear functions underscore the kinase’s role as an integrator of multiple signaling inputs that converge on the genomic machinery."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant MAPK1/ERK2 signaling is implicated in a broad spectrum of pathological conditions. Its dysregulation has been linked to processes driving tumor progression – such as epithelial‐to‐mesenchymal transition, enhanced angiogenesis via vascular endothelial growth factor upregulation, and altered adhesion and motility – and is also associated with cardiac hypertrophy, neurodegeneration (including aberrant mitophagy in Parkinson’s disease), inflammatory responses in diverse tissues, and even defective exosome biogenesis. These findings have not only illuminated the multifaceted roles of MAPK1 in disease pathogenesis but have also identified ERK2 as a potential therapeutic target whose modulation might restore normal cellular functions in oncology, cardiovascular medicine, neurobiology, and immunology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael B Fessler, Kenneth C Malcolm, Mark William Duncan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genomic and proteomic analysis of activation of the human neutrophil by lipopolysaccharide and its mediation by p38 mitogen-activated protein kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M200755200"}], "href": "https://doi.org/10.1074/jbc.M200755200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11943771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11943771"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Weiping Wang, Joan X Chen, Rong Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequential activation of the MEK-extracellular signal-regulated kinase and MKK3/6-p38 mitogen-activated protein kinase pathways mediates oncogenic ras-induced premature senescence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.22.10.3389-3403.2002"}], "href": "https://doi.org/10.1128/MCB.22.10.3389-3403.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11971971"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11971971"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Geum-Yi Kim, Stephen E Mercer, Daina Z Ewton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The stress-activated protein kinases p38 alpha and JNK1 stabilize p21(Cip1) by phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M201299200"}], "href": "https://doi.org/10.1074/jbc.M201299200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12058028"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12058028"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Marina Lasa, Sonya M Abraham, Christine Boucheron, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.22.22.7802-7811.2002"}], "href": "https://doi.org/10.1128/MCB.22.22.7802-7811.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12391149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12391149"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jin-Jing Pei, Heiko Braak, Wen-Lin An, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res Mol Brain Res (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0169-328x(02)00488-6"}], "href": "https://doi.org/10.1016/s0169-328x(02"}, {"type": "t", "text": "00488-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12531514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12531514"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Guru-Dutt Sharma, Jiucheng He, Haydee E P Bazan "}, {"type": "b", "children": [{"type": "t", "text": "p38 and ERK1/2 coordinate cellular migration and proliferation in epithelial wound healing: evidence of cross-talk activation between MAP kinase cascades."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M302650200"}], "href": "https://doi.org/10.1074/jbc.M302650200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12663671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12663671"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kyoung Seob Song, Won-Jae Lee, Kwang Chul Chung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin-1 beta and tumor necrosis factor-alpha induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M300096200"}], "href": "https://doi.org/10.1074/jbc.M300096200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12690113"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12690113"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Stuart M Pitson, Paul A B Moretti, Julia R Zebol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/cdg540"}], "href": "https://doi.org/10.1093/emboj/cdg540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14532121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14532121"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jian-Hui Zhu, Fengli Guo, John Shelburne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Localization of phosphorylated ERK/MAP kinases to mitochondria and autophagosomes in Lewy body diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Pathol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1750-3639.2003.tb00478.x"}], "href": "https://doi.org/10.1111/j.1750-3639.2003.tb00478.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14655753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14655753"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Monideepa Roy, Zhigang Li, David B Sacks "}, {"type": "b", "children": [{"type": "t", "text": "IQGAP1 binds ERK2 and modulates its activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308405200"}], "href": "https://doi.org/10.1074/jbc.M308405200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14970219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14970219"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Stefania Catalano, Loredana Mauro, Stefania Marsico, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leptin induces, via ERK1/ERK2 signal, functional activation of estrogen receptor alpha in MCF-7 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M313191200"}], "href": "https://doi.org/10.1074/jbc.M313191200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14985328"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14985328"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Paolo Calabro, Ismael Samudio, James T Willerson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.CIR.0000147825.97879.E7"}], "href": "https://doi.org/10.1161/01.CIR.0000147825.97879.E7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15545519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15545519"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Sridevi Devaraj, Senthil K Venugopal, Uma Singh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hyperglycemia induces monocytic release of interleukin-6 via induction of protein kinase c-{alpha} and -{beta}."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/diabetes.54.1.85"}], "href": "https://doi.org/10.2337/diabetes.54.1.85"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15616014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15616014"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Ping-Yuan Wang, Jian Weng, Richard G W Anderson "}, {"type": "b", "children": [{"type": "t", "text": "OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1107710"}], "href": "https://doi.org/10.1126/science.1107710"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15746430"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15746430"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Silvia Svegliati, Raffaella Cancello, Paola Sambo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Platelet-derived growth factor and reactive oxygen species (ROS) regulate Ras protein levels in primary human fibroblasts via ERK1/2. Amplification of ROS and Ras in systemic sclerosis fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M502851200"}], "href": "https://doi.org/10.1074/jbc.M502851200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16081426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16081426"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Megan Fabbro, Bin-Bing Zhou, Mikiko Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2005.09.003"}], "href": "https://doi.org/10.1016/j.devcel.2005.09.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16198290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16198290"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Sudha K Shenoy, Matthew T Drake, Christopher D Nelson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M506576200"}], "href": "https://doi.org/10.1074/jbc.M506576200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16280323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16280323"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Diane Gesty-Palmer, Minyong Chen, Eric Reiter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M513380200"}], "href": "https://doi.org/10.1074/jbc.M513380200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16492667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16492667"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Ilias Mylonis, Georgia Chachami, Martina Samiotaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of MAPK phosphorylation sites and their role in the localization and activity of hypoxia-inducible factor-1alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M605058200"}], "href": "https://doi.org/10.1074/jbc.M605058200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16954218"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16954218"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Elizabeth A Bolan, Bronwyn Kivell, Vanaja Jaligam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "D2 receptors regulate dopamine transporter function via an extracellular signal-regulated kinases 1 and 2-dependent and phosphoinositide 3 kinase-independent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.106.027763"}], "href": "https://doi.org/10.1124/mol.106.027763"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17267664"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17267664"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "S Meloche, J Pouysségur "}, {"type": "b", "children": [{"type": "t", "text": "The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1210414"}], "href": "https://doi.org/10.1038/sj.onc.1210414"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17496918"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17496918"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Yongfeng Fan, Jianqin Ye, Fanxia Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin-6 stimulates circulating blood-derived endothelial progenitor cell angiogenesis in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cereb Blood Flow Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.jcbfm.9600509"}], "href": "https://doi.org/10.1038/sj.jcbfm.9600509"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17519976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17519976"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Dolores M Cortez, Marc D Feldman, Srinivas Mummidi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-beta , NF-kappaB, and AP-1 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Heart Circ Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpheart.00928.2007"}], "href": "https://doi.org/10.1152/ajpheart.00928.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17921324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17921324"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Nik Sawe, Gary Steinberg, Heng Zhao "}, {"type": "b", "children": [{"type": "t", "text": "Dual roles of the MAPK/ERK1/2 cell signaling pathway after stroke."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jnr.21604"}], "href": "https://doi.org/10.1002/jnr.21604"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18189318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18189318"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Sandra Feldt, Wendy W Batenburg, Istvan Mazak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prorenin and renin-induced extracellular signal-regulated kinase 1/2 activation in monocytes is not blocked by aliskiren or the handle-region peptide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/HYPERTENSIONAHA.107.101444"}], "href": "https://doi.org/10.1161/HYPERTENSIONAHA.107.101444"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18212269"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18212269"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "A Seth, Fang Yan, D Brent Polk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00202.2007"}], "href": "https://doi.org/10.1152/ajpgi.00202.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18292183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18292183"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Seonhoe Kim, Ui Jin Lee, Mi Na Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M800186200"}], "href": "https://doi.org/10.1074/jbc.M800186200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18456660"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18456660"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Ruben K Dagda, Jianhui Zhu, Scott M Kulich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrially localized ERK2 regulates mitophagy and autophagic cell stress: implications for Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/auto.6458"}], "href": "https://doi.org/10.4161/auto.6458"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18594198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18594198"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Dana Chuderland, Alexander Konson, Rony Seger "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of a general nuclear translocation signal in signaling proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2008.08.007"}], "href": "https://doi.org/10.1016/j.molcel.2008.08.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18760948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18760948"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Kristina Lorenz, Joachim P Schmitt, Eva M Schmitteckert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.1893"}], "href": "https://doi.org/10.1038/nm.1893"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19060905"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19060905"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "J Dai, L Peng, K Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2009.189"}], "href": "https://doi.org/10.1038/onc.2009.189"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19597469"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19597469"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Katie L Pricola, Nastaran Z Kuhn, Hana Haleem-Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin-6 maintains bone marrow-derived mesenchymal stem cell stemness by an ERK1/2-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.22289"}], "href": "https://doi.org/10.1002/jcb.22289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19650110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19650110"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Shaohui Hu, Zhi Xie, Akishi Onishi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.08.037"}], "href": "https://doi.org/10.1016/j.cell.2009.08.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19879846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19879846"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Haitao Ji, Ji Wang, Heinz Nika, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EGF-induced ERK activation promotes CK2-mediated disassociation of alpha-Catenin from beta-Catenin and transactivation of beta-Catenin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2009.09.034"}], "href": "https://doi.org/10.1016/j.molcel.2009.09.034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19941816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19941816"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Q K Y Chan, H-M Lam, C-F Ng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of GPR30 inhibits the growth of prostate cancer cells through sustained activation of Erk1/2, c-jun/c-fos-dependent upregulation of p21, and induction of G(2) cell-cycle arrest."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2010.20"}], "href": "https://doi.org/10.1038/cdd.2010.20"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20203690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20203690"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Sejeong Shin, Christopher A Dimitri, Sang-Oh Yoon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERK2 but not ERK1 induces epithelial-to-mesenchymal transformation via DEF motif-dependent signaling events."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2010.02.020"}], "href": "https://doi.org/10.1016/j.molcel.2010.02.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20385094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20385094"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Audrey Carriere, Yves Romeo, Hugo A Acosta-Jaquez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERK1/2 phosphorylate Raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.159046"}], "href": "https://doi.org/10.1074/jbc.M110.159046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21071439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21071439"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Karin Wuertz, Nam Vo, Dimitris Kletsas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inflammatory and catabolic signalling in intervertebral discs: the roles of NF-κB and MAP kinases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Cell Mater (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.22203/ecm.v023a08"}], "href": "https://doi.org/10.22203/ecm.v023a08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22354461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22354461"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Xiaowen Liu, Bo Ma, Asrar B Malik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.2258"}], "href": "https://doi.org/10.1038/ni.2258"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22447027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22447027"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Rana Al-Sadi, Shuhong Guo, Dongmei Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TNF-α modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2013.09.001"}], "href": "https://doi.org/10.1016/j.ajpath.2013.09.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24121020"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24121020"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Yuko Hirota, Shun-ichi Yamashita, Yusuke Kurihara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitophagy is primarily due to alternative autophagy and requires the MAPK1 and MAPK14 signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2015.1023047"}], "href": "https://doi.org/10.1080/15548627.2015.1023047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25831013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25831013"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Amrita Datta, Hogyoung Kim, Madhu Lal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Manumycin A suppresses exosome biogenesis and secretion via targeted inhibition of Ras/Raf/ERK1/2 signaling and hnRNP H1 in castration-resistant prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2017.08.020"}], "href": "https://doi.org/10.1016/j.canlet.2017.08.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28844715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28844715"}]}]}]}