{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:24:08Z","timestamp":1789957448176,"version":"4.0.1"},"reference-count":87,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T00:00:00Z","timestamp":1602288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001869","name":"Academia Sinica","doi-asserted-by":"publisher","award":["[AS-SUMMIT-108], [AS-SUMMIT-109], [ASKPQ-109-BioMed]"],"award-info":[{"award-number":["[AS-SUMMIT-108], [AS-SUMMIT-109], [ASKPQ-109-BioMed]"]}],"id":[{"id":"10.13039\/501100001869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["[MOST-107-2320-B-001-016-MY3], [MOST-108-3114-Y-001-002]"],"award-info":[{"award-number":["[MOST-107-2320-B-001-016-MY3], [MOST-108-3114-Y-001-002]"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thousand and one kinases (TAOKs) are members of the MAP kinase kinase kinase (MAP3K) family. Three members of this subfamily, TAOK1, 2, and 3, have been identified in mammals. It has been shown that TAOK1, 2 and 3 regulate the p38 MAPK and Hippo signaling pathways, while TAOK 1 and 2 modulate the SAPK\/JNK cascade. Furthermore, TAOKs are involved in additional interactions with other cellular proteins and all of these pathways modulate vital physiological and pathophysiological responses in cells and tissues. Dysregulation of TAOK-related pathways is implicated in the development of diseases including inflammatory and immune disorders, cancer and drug resistance, and autism and Alzheimer\u2019s diseases. This review collates current knowledge concerning the roles of TAOKs in protein\u2013protein interaction, signal transduction, physiological regulation, and pathogenesis and summarizes the recent development of TAOK-specific inhibitors that have the potential to ameliorate TAOKs\u2019 effects in pathological situations.<\/jats:p>","DOI":"10.3390\/ijms21207463","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T22:02:02Z","timestamp":1602626522000},"page":"7463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["The Diverse Roles of TAO Kinases in Health and Diseases"],"prefix":"10.3390","volume":"21","author":[{"given":"Chih-Yeu","family":"Fang","sequence":"first","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Ching","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8529-9213","authenticated-orcid":false,"given":"Michael","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 115, Taiwan"},{"name":"Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0474-9935","authenticated-orcid":false,"given":"Yu-Chan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Radiological Science, National Yang-Ming University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,10]]},"reference":[{"key":"ref_1","first-page":"153","article-title":"Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions","volume":"22","author":"Pearson","year":"2001","journal-title":"Endocr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.1002\/j.1460-2075.1992.tb05587.x","article-title":"The Protein-Kinase Homolog Ste20p Is Required to Link the Yeast Pheromone Response G-Protein Beta-Gamma Subunits to Downstream Signaling Components","volume":"11","author":"Leberer","year":"1992","journal-title":"Embo J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1073\/pnas.90.2.452","article-title":"A Dominant Truncation Allele Identifies a Gene, Ste20, That Encodes a Putative Protein-Kinase Necessary for Mating in Saccharomyces-Cerevisiae","volume":"90","author":"Ramer","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28625","DOI":"10.1074\/jbc.273.44.28625","article-title":"Isolation of TAO1, a protein kinase that activates MEKs in stress-activated protein kinase cascades","volume":"273","author":"Hutchison","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"28803","DOI":"10.1074\/jbc.274.40.28803","article-title":"Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase\/extracellular signal-regulated kinase kinase binding domain","volume":"274","author":"Chen","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"33287","DOI":"10.1074\/jbc.274.47.33287","article-title":"Human JIK, a novel member of the STE20 kinase family that inhibits JNK and is negatively regulated by epidermal growth factor","volume":"274","author":"Tassi","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4311","DOI":"10.1074\/jbc.275.6.4311","article-title":"PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and regulates actin cytoskeletal organization","volume":"275","author":"Moore","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6129","DOI":"10.1038\/sj.onc.1206605","article-title":"Comparative studies of a new subfamily of human Ste20-like kinases: Homodimerization, subcellular localization, and selective activation of MKK3 and p38","volume":"22","author":"Yustein","year":"2003","journal-title":"Oncogene"},{"key":"ref_9","first-page":"a011254","article-title":"MAP Kinase Pathways","volume":"4","author":"Morrison","year":"2012","journal-title":"Csh Perspect Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1038\/sj.onc.1210409","article-title":"Role of mitogen-activated protein kinase kinase kinases in signal integration","volume":"26","author":"Cuevas","year":"2007","journal-title":"Oncogene"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.cell.2015.10.044","article-title":"Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer","volume":"163","author":"Yu","year":"2015","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrm2221","article-title":"Filling out the Hippo pathway","volume":"8","author":"Saucedo","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1038\/sj.emboj.7601668","article-title":"TAO kinases mediate activation of p38 in response to DNA damage","volume":"26","author":"Raman","year":"2007","journal-title":"Embo J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"22278","DOI":"10.1074\/jbc.M301173200","article-title":"TAO (thousand-and-one amino acid) protein kinases mediate signaling from carbachol to p38 mitogen-activated protein kinase and ternary complex factors","volume":"278","author":"Chen","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16070","DOI":"10.1074\/jbc.M100681200","article-title":"Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2","volume":"276","author":"Chen","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ceb.2007.02.001","article-title":"The JNK signal transduction pathway","volume":"19","author":"Weston","year":"2007","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.bbapap.2009.11.002","article-title":"c-Jun N-terminal kinase (JNK) signaling: Recent advances and challenges","volume":"1804","author":"Bogoyevitch","year":"2010","journal-title":"Bba-Proteins. Proteom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7317","DOI":"10.1074\/jbc.M513769200","article-title":"Prostate-derived sterile 20-like kinase 2 (PSK2) regulates apoptotic morphology via C-jun N-terminal kinase and Rho kinase-1","volume":"281","author":"Zihni","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6484","DOI":"10.1074\/jbc.M608336200","article-title":"Prostate-derived sterile 20-like kinase 1-alpha induces apoptosis\u2014JNK- and caspase-dependent nuclear localization is a requirement for membrane blebbing","volume":"282","author":"Zihni","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1006\/bbrc.2000.3244","article-title":"Cloning of DPK, a novel dendritic cell-derived protein kinase activating the ERK1\/ERK2 and JNK\/SAPK pathways","volume":"274","author":"Zhang","year":"2000","journal-title":"Biochem. Bioph. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/ncb1258","article-title":"Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance","volume":"7","author":"MacKeigan","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kapfhamer, D., King, I., Zou, M.E., Lim, J.P., Heberlein, U., and Wolf, F.W. (2012). JNK Pathway Activation Is Controlled by Tao\/TAOK3 to Modulate Ethanol Sensitivity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050594"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1152\/physrev.00005.2014","article-title":"The Biology of Yap\/Taz: Hippo Signaling and Beyond","volume":"94","author":"Piccolo","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1101\/gad.210773.112","article-title":"The Hippo pathway: Regulators and regulations","volume":"27","author":"Yu","year":"2013","journal-title":"Gene Dev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.devcel.2011.08.028","article-title":"Tao-1 Phosphorylates Hippo\/MST Kinases to Regulate the Hippo-Salvador-Warts Tumor Suppressor Pathway","volume":"21","author":"Boggiano","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.devcel.2011.09.012","article-title":"The Sterile 20-like Kinase Tao-1 Controls Tissue Growth by Regulating the Salvador-Warts-Hippo Pathway","volume":"21","author":"Poon","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.molcel.2016.10.034","article-title":"Characterization of Hippo Pathway Components by Gene Inactivation","volume":"64","author":"Plouffe","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8357","DOI":"10.1038\/ncomms9357","article-title":"MAP4K family kinases act in parallel to MST1\/2 to activate LATS1\/2 in the Hippo pathway","volume":"6","author":"Meng","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"18085","DOI":"10.1074\/jbc.M213064200","article-title":"The prostate-derived sterile 20-like kinase (PSK) regulates microtubule organization and stability","volume":"278","author":"Mitsopoulos","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5090","DOI":"10.1093\/emboj\/cdg447","article-title":"MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK\/PAR-1","volume":"22","author":"Timm","year":"2003","journal-title":"Embo J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1242\/jcs.068726","article-title":"Tao-1 is a negative regulator of microtubule plus-end growth","volume":"123","author":"Liu","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s40478-018-0539-8","article-title":"A new TAO kinase inhibitor reduces tau phosphorylation at sites associated with neurodegeneration in human tauopathies","volume":"6","author":"Giacomini","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1158\/1535-7163.MCT-17-0077","article-title":"Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells","volume":"16","author":"Koo","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/nn.3141","article-title":"Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex","volume":"15","author":"Rosario","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"30161","DOI":"10.1074\/jbc.M111.228320","article-title":"Prostate-derived Sterile 20-like Kinases (PSKs\/TAOKs) Are Activated in Mitosis and Contribute to Mitotic Cell Rounding and Spindle Positioning","volume":"286","author":"Wojtala","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"130108","DOI":"10.1098\/rsob.130108","article-title":"TAO1 kinase maintains chromosomal stability by facilitating proper congression of chromosomes","volume":"4","author":"Shrestha","year":"2014","journal-title":"Open Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15418","DOI":"10.1074\/jbc.M112.448183","article-title":"Prostate-derived Sterile 20-like Kinases (PSKs\/TAOKs) Phosphorylate Tau Protein and Are Activated in Tangle-bearing Neurons in Alzheimer Disease","volume":"288","author":"Tavares","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Garg, R., Koo, C.Y., Infante, E., Giacomini, C., Ridley, A.J., and Morris, J.D.H. (2020). Rnd3 interacts with TAO kinases and contributes to mitotic cell rounding and spindle positioning. J. Cell Sci., 133.","DOI":"10.1242\/jcs.235895"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1091\/mbc.e07-07-0730","article-title":"Spred1 and TESK1--two new interaction partners of the kinase MARKK\/TAO1 that link the microtubule and actin cytoskeleton","volume":"19","author":"Johne","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.neuron.2014.10.025","article-title":"MST3 kinase phosphorylates TAO1\/2 to enable Myosin Va function in promoting spine synapse development","volume":"84","author":"Ultanir","year":"2014","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.neuron.2016.12.006","article-title":"TAOK2 Kinase Mediates PSD95 Stability and Dendritic Spine Maturation through Septin7 Phosphorylation","volume":"93","author":"Yadav","year":"2017","journal-title":"Neuron"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1038\/s41380-018-0025-5","article-title":"Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling","volume":"24","author":"Richter","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.neuron.2007.08.020","article-title":"Activity-induced protocadherin arcadlin regulates dendritic spine number by triggering N-cadherin endocytosis via TAO2 beta and p38 MAP kinases","volume":"56","author":"Yasuda","year":"2007","journal-title":"Neuron"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/cmi.2017.158","article-title":"TAOK1 negatively regulates IL-17-mediated signaling and inflammation","volume":"15","author":"Zhang","year":"2018","journal-title":"Cell Mol. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.molimm.2020.04.006","article-title":"TAOK1 positively regulates TLR4-induced inflammatory responses by promoting ERK1\/2 activation in macrophages","volume":"122","author":"Zhu","year":"2020","journal-title":"Mol. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/ni.3657","article-title":"Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10","volume":"18","author":"Hammad","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3431","DOI":"10.4049\/jimmunol.1800284","article-title":"TAOK3 Regulates Canonical TCR Signaling by Preventing Early SHP-1-Mediated Inactivation of LCK","volume":"201","author":"Ormonde","year":"2018","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jdermsci.2017.03.018","article-title":"Generalized verrucosis and abnormal T cell activation due to homozygous TAOK2 mutation","volume":"87","author":"Ramot","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"28802","DOI":"10.1074\/jbc.M603627200","article-title":"Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated NF-kappa B activation\u2014TAO2 regulates TAK1 pathways","volume":"281","author":"HuangFu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"140161","DOI":"10.1098\/rsob.140161","article-title":"Drosophila gene tao-1 encodes proteins with and without a Ste20 kinase domain that affect cytoskeletal architecture and cell migration differently","volume":"5","author":"Pflanz","year":"2015","journal-title":"Open Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1101\/gr.254276.119","article-title":"A novel assay to screen siRNA libraries identifies protein kinases required for chromosome transmission","volume":"29","author":"Liskovykh","year":"2019","journal-title":"Genome Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8147","DOI":"10.1158\/0008-5472.CAN-05-3489","article-title":"Frequent alterations in the expression of serine\/threonine kinases in human cancers","volume":"66","author":"Capra","year":"2006","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lai, T.C., Fang, C.Y., Jan, Y.H., Hsieh, H.L., Yang, Y.F., Liu, C.Y., Chang, P.M.H., and Hsiao, M. (2020). Kinase shRNA screening reveals that TAOK3 enhances microtubule-targeted drug resistance of breast cancer cells via the NF-\u03baB signaling pathway. Cell Commun. Signal., in press.","DOI":"10.1186\/s12964-020-00600-2"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Schulte, I., Batty, E.M., Pole, J.C., Blood, K.A., Mo, S., Cooke, S.L., Ng, C., Howe, K.L., Chin, S.F., and Brenton, J.D. (2012). Structural analysis of the genome of breast cancer cell line ZR-75\u201330 identifies twelve expressed fusion genes. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-719"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00109-011-0831-6","article-title":"Comparative kinome analysis to identify putative colon tumor biomarkers","volume":"90","author":"Hennig","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Li, Y., He, C.L., Li, W.X., Zhang, R.X., and Duan, Y. (2020). Transcriptome analysis reveals gender-specific differences in overall metabolic response of male and female patients in lung adenocarcinoma. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0230796"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1158\/1535-7163.MCT-18-1011","article-title":"Target Deconvolution of a Multikinase Inhibitor with Antimetastatic Properties Identifies TAOK3 as a Key Contributor to a Cancer Stem Cell-Like Phenotype","volume":"18","author":"Bian","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Romanuik, T.L., Wang, G., Holt, R.A., Jones, S.J.M., Marra, M.A., and Sadar, M.D. (2009). Identification of novel androgen-responsive genes by sequencing of LongSAGE libraries. BMC Genom., 10.","DOI":"10.1186\/1471-2164-10-476"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15451","DOI":"10.18632\/oncotarget.24503","article-title":"Replication-incompetent gammaretroviral and lentiviral vector-based insertional mutagenesis screens identify prostate cancer progression genes","volume":"9","author":"Bii","year":"2018","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.1021\/acs.jproteome.6b00613","article-title":"Activity-Based Protein Profiling Shows Heterogeneous Signaling Adaptations to BRAF Inhibition","volume":"15","author":"Sharma","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1182\/blood-2009-07-234229","article-title":"Wide diversity of PAX5 alterations in B-ALL: A Groupe Francophone de Cytogenetique Hematologique study","volume":"115","author":"Coyaud","year":"2010","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1056\/NEJMoa075974","article-title":"Association between microdeletion and microduplication at 16p11.2 and autism","volume":"358","author":"Weiss","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ajhg.2019.05.005","article-title":"De Novo Variants in TAOK1 Cause Neurodevelopmental Disorders","volume":"105","author":"Trinh","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zach, S., Felk, S., and Gillardon, F. (2010). Signal Transduction Protein Array Analysis Links LRRK2 to Ste20 Kinases and PKC Zeta That Modulate Neuronal Plasticity. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013191"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/bies.200900163","article-title":"Mechanisms in dominant parkinsonism: The toxic triangle of LRRK2, alpha-synuclein, and tau","volume":"32","author":"Taymans","year":"2010","journal-title":"Bioessays"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Li, J.H., Liu, Z.J., Wang, L.L., Xu, H.Y., and Wang, Y.L. (2019). Thousand and one kinase 1 protects MCAO-induced cerebral ischemic stroke in rats by decreasing apoptosis and pro-inflammatory factors. Biosci. Rep., 39.","DOI":"10.1042\/BSR20190749"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Li, Z., Oh, H., Cung, M., Marquez, S.J., Sun, J., Hammad, H., Janssens, S., Pouliot, P., Lambrecht, B.N., and Yang, Y.S. (2020). TAOK3 is a MAP3K contributing to osteoblast differentiation and skeletal mineralization. Biochem. Biophys. Res. Commun.","DOI":"10.1016\/j.bbrc.2020.07.060"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"37509","DOI":"10.1038\/srep37509","article-title":"miR-706 inhibits the oxidative stress-induced activation of PKCalpha\/TAOK1 in liver fibrogenesis","volume":"6","author":"Yin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Jing, H., Zhang, X.Y., Luo, K., Luo, Q.C., Yin, M., Wang, W., Zhu, Z.Q., Zheng, J.H., and He, X.M. (2020). miR-381-abundant small extracellular vesicles derived from kartogenin-preconditioned mesenchymal stem cells promote chondrogenesis of MSCs by targeting TAOK1. Biomaterials, 231.","DOI":"10.1016\/j.biomaterials.2019.119682"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e58471","DOI":"10.1371\/journal.pone.0058471","article-title":"The miR-183\/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma","volume":"8","author":"Patel","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Balashanmugam, M.V., Shivanandappa, T.B., Nagarethinam, S., Vastrad, B., and Vastrad, C. (2019). Analysis of Differentially Expressed Genes in Coronary Artery Disease by Integrated Microarray Analysis. Biomolecules, 10.","DOI":"10.3390\/biom10010035"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41408-020-0309-2","article-title":"A high definition picture of somatic mutations in chronic lymphoproliferative disorder of natural killer cells","volume":"10","author":"Gasparini","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_73","first-page":"1","article-title":"A role for Taok2 in Listeria monocytogenes vacuolar escape","volume":"10","author":"Quereda","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/j.pain.2014.05.032","article-title":"TAOK3, a novel genome-wide association study locus associated with morphine requirement and postoperative pain in a retrospective pediatric day surgery population","volume":"155","author":"Li","year":"2014","journal-title":"Pain"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jpainsymman.2018.07.011","article-title":"Single-Nucleotide Polymorphisms in TAOK3 Are Associated With High Opioid Requirement for Pain Management in Patients With Advanced Cancer Admitted to a Tertiary Palliative Care Unit","volume":"56","author":"Gutteridge","year":"2018","journal-title":"J. Pain Symptom Manag."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1016\/j.pain.2014.08.008","article-title":"Challenges and cautions with small and retrospective postoperative pain genome-wide association studies with TAOK3","volume":"155","author":"Sadhasivam","year":"2014","journal-title":"Pain"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1097\/j.pain.0000000000000946","article-title":"Pain versus analgesia: TAOK3 as a pharmacogene Reply","volume":"158","author":"Matic","year":"2017","journal-title":"Pain"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1601-183X.2012.00834.x","article-title":"Taok2 controls behavioral response to ethanol in mice","volume":"12","author":"Kapfhamer","year":"2013","journal-title":"Genes Brain Behav."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1080\/15592294.2015.1080411","article-title":"Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood","volume":"10","author":"Huang","year":"2015","journal-title":"Epigenetics Us"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.antiviral.2015.04.001","article-title":"TAOK3 phosphorylates the methylenecyclopropane nucleoside MBX 2168 to its monophosphate","volume":"119","author":"Cardinale","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.bbrc.2011.12.044","article-title":"Identification of host cell proteins which interact with herpes simplex virus type 1 tegument protein pUL37","volume":"417","author":"Kelly","year":"2012","journal-title":"Biochem. Bioph. Res. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1745-7270.2006.00173.x","article-title":"Crystal structure of the MAP3K TAO2 kinase domain bound by an inhibitor staurosporine","volume":"38","author":"Zhou","year":"2006","journal-title":"Acta Biochimica et Biophysica Sinica"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1021\/jm8005806","article-title":"Toward the Development of a Potent and Selective Organoruthenium Mammalian Sterile 20 Kinase Inhibitor","volume":"52","author":"Anand","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1016\/j.bmcl.2016.07.016","article-title":"Discovery of novel TAOK2 inhibitor scaffolds from high-throughput screening","volume":"26","author":"Piala","year":"2016","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5244","DOI":"10.1021\/acs.jcim.9b00684","article-title":"Investigation of crystal structures in structure-based virtual screening for protein kinase inhibitors","volume":"59","author":"Chen","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1080\/14756366.2019.1673745","article-title":"Design, synthesis and biological evaluation of novel 1h-1,2,4-triazole, benzothiazole and indazole-based derivatives as potent fgfr1 inhibitors viafragment-based virtual screening","volume":"35","author":"Liu","year":"2020","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1016\/j.str.2004.07.021","article-title":"Crystal structure of the tao2 kinase domain: Activation and specificity of a ste20p map3k","volume":"12","author":"Zhou","year":"2004","journal-title":"Structure"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/20\/7463\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:18:56Z","timestamp":1760177936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/20\/7463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,10]]},"references-count":87,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ijms21207463"],"URL":"https:\/\/doi.org\/10.3390\/ijms21207463","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,10]]}}}