{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe provided studies highlight the multifaceted signaling role of DOK5—a membrane‐associated adaptor protein—in diverse biological contexts and disease states. In a glaucoma mouse model, DOK5 is negatively regulated by miR-141-3p, leading to an attenuation of the mitogen-activated protein kinase (MAPK) signaling cascade. This suppression results in decreased retinal vascular epithelial cell proliferation and angiogenesis while promoting apoptosis of retinal ganglion cells, thereby mitigating retinal neovascularization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of fibrosis, particularly in systemic sclerosis, DOK5 is upregulated in fibroblasts by insulin-like growth factor binding protein-5 (IGFBP-5). This upregulation, mediated through MAPK pathway activation and subsequent nuclear translocation, contributes to fibroblast proliferation and increased extracellular matrix deposition, ultimately promoting tissue fibrosis in both skin and lung tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDuring cardiomyocyte differentiation, DOK5 expression is tightly controlled by the transcription factor FOXO3a within the PI3K/PKB signaling pathway. FOXO3a normally represses DOK5 via direct binding to its promoter; however, relieving this repression facilitates increased DOK5 levels that are associated with enhanced differentiation of cardiac cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn sensory neurons, DOK5 also plays a crucial role in neuroprotection. By interacting with the TrkC receptor in the presence of neurotrophin-3 (NT-3), DOK5 is fundamental for blocking TrkC-induced apoptosis. This protective mechanism involves modulation of caspase-3 activity, thereby favoring neuronal survival during development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, emerging evidence in bone tissue engineering suggests that DOK5 contributes to osteoblast proliferation and differentiation. Although this role is still under investigation, its potential impact on bone regeneration underscores DOK5’s versatile function in regulating cell growth and differentiation across various tissue types."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Li-Qiong Zhang, Hao Cui, Yong-Bin Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-141-3p inhibits retinal neovascularization and retinal ganglion cell apoptosis in glaucoma mice through the inactivation of Docking protein 5-dependent mitogen-activated protein kinase signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.27549"}], "href": "https://doi.org/10.1002/jcp.27549"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30515784"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30515784"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hidekata Yasuoka, Yukie Yamaguchi, Carol A Feghali-Bostwick "}, {"type": "b", "children": [{"type": "t", "text": "The membrane-associated adaptor protein DOK5 is upregulated in systemic sclerosis and associated with IGFBP-5-induced fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0087754"}], "href": "https://doi.org/10.1371/journal.pone.0087754"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24551065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24551065"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jianyan Wen, Qing Xia, Cheng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dok-5 is involved in cardiomyocyte differentiation through PKB/FOXO3a pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2009.09.015"}], "href": "https://doi.org/10.1016/j.yjmcc.2009.09.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19800350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19800350"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yanfang Pan, Jing Zhang, Wei Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dok5 is involved in the signaling pathway of neurotrophin-3 against TrkC-induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2013.08.006"}], "href": "https://doi.org/10.1016/j.neulet.2013.08.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23954828"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23954828"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Liang Xu, Junguo Wu, Yueming Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dok5 regulates proliferation and differentiation of osteoblast via canonical Wnt/β-catenin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Musculoskelet Neuronal Interact (2022)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35234166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35234166"}]}]}]}