{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProtein tyrosine phosphatase receptor type R (PTPRR) is a dual‐function enzyme that predominantly acts as a negative regulator of intracellular signaling cascades. Structural studies have revealed that PTPRR harbors an open WPD loop—a key catalytic feature that distinguishes its regulatory properties compared with other phosphatases and supports its ability to dephosphorylate mitogen‐activated protein kinases (MAPKs)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the nervous system, PTPRR negatively modulates extracellular signal–regulated kinase (ERK) signaling. Its expression appears to be transcriptionally regulated by androgens, and genetic variations in PTPRR, as well as associations with altered resting-state brain activity, have been linked to major depressive disorder and suicidal behavior, suggesting that PTPRR may influence neuropsychiatric endophenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn oncological contexts, epigenetic and expression alterations of PTPRR contribute to the dysregulation of key signaling pathways that govern cell proliferation and differentiation. In cervical cancer, DNMT3B‐mediated promoter methylation silences PTPRR, thereby releasing its inhibitory effect on p44/42 MAPK signaling and facilitating metastasis; similar methylation events have been observed in adenocarcinomas of the uterine cervix."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In ovarian cancer, PTPRR serves as a tumor suppressor by dephosphorylating β–catenin at Tyr‑142—a modification critical for determining its transcriptional activity—which, when restored through ectopic expression, delays cancer cell growth both in vitro and in vivo."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, in lung adenocarcinoma, re-expression of PTPRR inhibits ERK1/2 phosphorylation, leading to reduced cell proliferation and migration, and in castration-resistant prostate cancer, PTPRR has surfaced as a hub gene whose high expression correlates with a poor prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In contrast, investigations in colorectal carcinoma have reported high protein expression levels of PTPRR in malignant, adenomatous, and normal colon tissues, suggesting that the regulation of PTPRR and its precise role in tumor progression may be context dependent."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jeyanthy Eswaran, Jens Peter von Kries, Brian Marsden, et al. 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