{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts mention SNORD115‑38, the collective body of work instead outlines the diverse functions of P‐Rex1 (phosphatidylinositol‑3,4,5‑trisphosphate‑dependent Rac exchange factor 1). In cancer models, P‑Rex1 operates as a key modulator of Rac1 signaling to control actin cytoskeletal reorganization, cell migration, and invasion. In PIK3CA mutant and HER2‐amplified breast cancers, for example, P‑Rex1 functions downstream of PI3K to regulate not only the canonical AKT pathway but also a Rac1/ERK cascade that governs apoptosis and therapeutic sensitivity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, multiple studies underscore the essential role of P‑Rex1 in immune regulation. In neutrophils and other leukocytes, P‑Rex1 mediates guanine nucleotide exchange on Rac GTPases in response to chemoattractants and GPCR signals, thereby promoting proper integrin activation, adhesion, chemotaxis, and reactive oxygen species (ROS) production. These studies reveal that P‑Rex1’s coordinated regulation of Rac1 and Rac2 is crucial for processes such as slow leukocyte rolling and transmigration during inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional roles for P‑Rex1 have been identified in non‐immune contexts. In adipocytes, for instance, P‑Rex1 facilitates PI3K‑dependent membrane ruffling that contributes to GLUT4 trafficking at submaximal insulin concentrations, linking cytoskeletal dynamics to metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Moreover, aberrant P‑Rex1 signaling has been implicated in neurodevelopmental disorders, as genetic variations affecting its function in the hippocampus lead to deficits in synaptic plasticity and behaviors reminiscent of autism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Finally, studies in lung and cardiac models indicate that P‑Rex1 contributes to pathological remodeling such as pulmonary and cardiac fibrosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Colin R Lindsay, Samuel Lawn, Andrew D Campbell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P-Rex1 is required for efficient melanoblast migration and melanoma metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms1560"}], "href": "https://doi.org/10.1038/ncomms1560"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22109529"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22109529"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hiromichi Ebi, Carlotta Costa, Anthony C Faber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1314124110"}], "href": "https://doi.org/10.1073/pnas.1314124110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24327733"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24327733"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hadir Marei, Alejandro Carpy, Anna Woroniuk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms10664"}], "href": "https://doi.org/10.1038/ncomms10664"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26887924"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26887924"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nuthasuda Srijakotre, Heng-Jia Liu, Max Nobis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PtdIns(3,4,5)P"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "3"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": "-dependent Rac exchanger 1 (P-Rex1) promotes mammary tumor initiation and metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2006445117"}], "href": "https://doi.org/10.1073/pnas.2006445117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33097662"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33097662"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Heidi C E Welch, Alison M Condliffe, Laura J Milne, et al. 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