{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTAOK2, a member of the thousand‐and‐one amino acid kinases, functions as a versatile signal transducer in neuronal cells. In response to extracellular cues such as carbachol and osmotic stress, TAOK2 relays signals to key MAP kinase cascades—for example, activating p38 and JNK pathways—thereby modulating cellular stress responses. Importantly, TAOK2 is implicated in neurodevelopmental processes; it is located within the 16p11.2 genetic region associated with autism and has been shown to be essential for basal dendrite formation in cortical pyramidal neurons by linking Neuropilin 1/Semaphorin 3A signals to downstream JNK activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n \nDis parturient in cytoskeletal organization and cell division, TAOK2 additionally phosphorylates tau protein on numerous residues that are critical for microtubule binding—a modification that may contribute to neurodegenerative pathology such as Alzheimer disease. TAOK2 also localizes to centrosomes during mitosis, where its inhibition promotes mitotic delay, centrosome amplification, and multipolar spindle formation, thereby preferentially triggering mitotic catastrophe in cancer cells. Moreover, TAOK2 functions as an endoplasmic reticulum–microtubule tether via its transmembrane domain and a C-terminal microtubule-binding region, ensuring proper ER morphology and dynamic interactions with the microtubule cytoskeleton during cell division."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n \nTAOK2 further modulates pathogenic and oncogenic processes. In the context of viral infection, a specific circular RNA (circSIAE) has been shown to attenuate CVB3 replication by sponging miR-331-3p, which targets TAOK2, thereby indirectly restraining viral proliferation. Complementarily, TAOK2 acts as a tumor suppressor by interacting with core components of the Hippo signaling pathway—binding to and phosphorylating kinases such as LATS1—which culminates in the attenuation of the oncogenic mediator YAP1. This modulation of Hippo signaling reduces cell proliferation and migration, correlating reduced TAOK2 expression with poorer patient survival in several cancer types."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhu Chen, Malavika Raman, Linda Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TAO (thousand-and-one amino acid) protein kinases mediate signaling from carbachol to p38 mitogen-activated protein kinase and ternary complex factors."}]}, {"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.M301173200"}], "href": "https://doi.org/10.1074/jbc.M301173200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12665513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12665513"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wei-Chun Huangfu, Emily Omori, Shizuo Akira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated NF-kappaB activation: TAO2 regulates TAK1 pathways."}]}, {"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.M603627200"}], "href": "https://doi.org/10.1074/jbc.M603627200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16893890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16893890"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ravinesh A Kumar, Christian R Marshall, Judith A Badner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association and mutation analyses of 16p11.2 autism candidate genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0004582"}], "href": "https://doi.org/10.1371/journal.pone.0004582"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19242545"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19242545"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Froylan Calderon de Anda, Ana Lucia Rosario, Omer Durak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn.3141"}], "href": "https://doi.org/10.1038/nn.3141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22683681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22683681"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ignatius A Tavares, Dona Touma, Steven Lynham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prostate-derived sterile 20-like kinases (PSKs/TAOKs) phosphorylate tau protein and are activated in tangle-bearing neurons in Alzheimer disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.448183"}], "href": "https://doi.org/10.1074/jbc.M112.448183"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23585562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23585562"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chuay-Yeng Koo, Caterina Giacomini, Marta Reyes-Corral, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-17-0077"}], "href": "https://doi.org/10.1158/1535-7163.MCT-17-0077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28830982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28830982"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kimya Nourbakhsh, Amy A Ferreccio, Matthew J Bernard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TAOK2 is an ER-localized kinase that catalyzes the dynamic tethering of ER to microtubules."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2021.11.015"}], "href": "https://doi.org/10.1016/j.devcel.2021.11.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34879262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34879262"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Qingru Yang, Yuhan Li, Yan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The circRNA circSIAE Inhibits Replication of Coxsackie Virus B3 by Targeting miR-331-3p and Thousand and One Amino-Acid Kinase 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Infect Microbiol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcimb.2021.779919"}], "href": "https://doi.org/10.3389/fcimb.2021.779919"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35141166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35141166"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xiao Ma, Fiona J Mandausch, Yuxin Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comprehensive split TEV based protein-protein interaction screening reveals TAOK2 as a key modulator of Hippo signalling to limit growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2023.110917"}], "href": "https://doi.org/10.1016/j.cellsig.2023.110917"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37813295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37813295"}]}]}]}