{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTensin2 (TNS2), also known as C1‐Ten, is a multidomain focal adhesion protein that functions as a physical and signaling bridge between the extracellular matrix and the actin cytoskeleton. Its unique domain architecture—including an N‐terminal C1 region, a central phosphatase motif, and C‐terminal SH2 and PTB domains—enables selective binding to diverse partners such as receptor tyrosine kinases, adaptor proteins, and scaffolds. These interactions, delineated by studies on its binding with Axl, DLC1, DISC1, and others, underscore its role as an intracellular signal-integrator."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its structural contributions, TNS2 acts as an intracellular protein tyrosine phosphatase that exerts negative control over key signaling cascades. Experimental evidence shows that its ectopic expression results in reduced phosphorylation and activity of Akt by dephosphorylating substrates within the PI3K/Akt pathway. In addition, TNS2 modulates insulin signaling through interactions with IRS-1 and has been implicated in regulating receptor-mediated events (for example, via Axl), thereby fine-tuning cellular survival and metabolic responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the cellular level, TNS2 importantly governs cell migration and tumorigenesis through its regulation of focal adhesion dynamics and interactions with tumor suppressors such as DLC1. While certain splicing variants (notably variant 3) have been associated with enhanced cell proliferation, motility, and hepatocarcinogenesis, loss-of-function studies indicate that decreased TNS2 levels lead to hyperactivation of oncogenic pathways. This duality suggests that TNS2 can serve either to suppress or, in particular contexts, foster cell transformation depending on the balance of its regulatory interactions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTNS2 also plays roles in diverse physiological and pathological contexts beyond oncogenesis. In the hematopoietic system, it modulates thrombopoietin receptor signaling influencing stem and progenitor cell proliferation. In kidney cells, its phosphatase activity targets nephrin—a key slit diaphragm protein—thereby redirecting downstream signaling to activate mTORC1 and promote podocyte hypertrophy, a process relevant to diabetic kidney disease. Moreover, regulatory mechanisms, such as p62-mediated sequestration that leads to TNS2 ubiquitination and degradation, along with observations linking its expression to chemotherapeutic sensitivity in pancreatic ductal adenocarcinoma, reinforce the multifaceted influence of TNS2 on cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sassan Hafizi, Filiz Alindri, Roger Karlsson, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Solution structure of tensin2 SH2 domain and its phosphotyrosine-independent interaction with DLC-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0021965"}], "href": "https://doi.org/10.1371/journal.pone.0021965"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21765928"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21765928"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kyung D Moon, Xiaoying Zhang, Qing Zhou, et al. 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