{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have shown that human-secreted Ly‐6/uPAR‐related protein‐2 (SLURP‐2) is a key regulator of epithelial cell growth and differentiation through its interaction with multiple cholinergic receptor subtypes. Structural investigations revealed that SLURP‐2 adopts a conserved “three‐finger” fold, and pharmacological studies demonstrated that it binds to a broad range of nicotinic acetylcholine receptor (nAChR) subunits—including α3, α4, α5, α7, β2, and β4. Functionally, SLURP‐2 modulates receptor activity in a concentration-dependent manner: it inhibits acetylcholine‐evoked currents at certain receptor assemblies (for example, at α3β2 and, to a lesser extent, α4β2 receptors) while enhancing current through α7 receptors at low doses. Moreover, SLURP‐2’s allosteric actions on muscarinic acetylcholine receptors (mAChRs) further contribute to its effects on keratinocyte proliferation by stimulating growth via α3β2-nAChR engagement and inhibiting it via α7-nAChR interaction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in normal epithelial physiology, SLURP‐2 has been evaluated for potential anticancer properties. Investigations have revealed that, as an endogenous antagonist of nAChRs, SLURP‐2—alongside its closely related protein SLURP‐1—can modulate key signaling pathways in human epithelial cancer cells, making these molecules promising targets for new anticancer therapies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWhile the functionalities of SLURP‐2 have been extensively elucidated in the context of epithelial cell regulation and cancer biology, other studies have focused on tissue-specific regulatory proteins in entirely different physiological processes. For instance, investigations into the testis-specific gene SPATA48 have provided insights into spermatogenesis and male infertility, underscoring that the regulatory roles of proteins can be highly context-dependent and tissue-specific."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "E N Lyukmanova, M A Shulepko, Z O Shenkarev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep30698"}], "href": "https://doi.org/10.1038/srep30698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27485575"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27485575"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "E N Lyukmanova, M L Bychkov, G V Sharonov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human secreted proteins SLURP-1 and SLURP-2 control the growth of epithelial cancer cells via interactions with nicotinic acetylcholine receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Pharmacol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bph.14194"}], "href": "https://doi.org/10.1111/bph.14194"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29505672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29505672"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "J Zhang, R Yan, C Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spermatogenesis-associated 48 is essential for spermatogenesis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Andrologia (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/and.13027"}], "href": "https://doi.org/10.1111/and.13027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29700843"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29700843"}]}]}]}