{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProtein kinase D2 (PRKD2) is emerging as a versatile signal transducer activated by a wide array of extracellular stimuli. Studies in human cancer cells have demonstrated that PRKD2 is stimulated by G‐protein–coupled receptor agonists—such as gastrin and neurotensin—and by oncogenic tyrosine kinases like Bcr‐Abl, thereby triggering downstream cascades that include nuclear translocation, NF‑κB and NFAT activation, and modulation of interferon receptor (IFNAR1) turnover. Moreover, genome‐wide association studies in chronic lymphocytic leukemia and related B‐cell disorders have identified common variants within the PRKD2 locus that are associated with increased disease susceptibility. In T lymphocytes, PRKD2 interacts with Src family kinases (e.g. Lck) to influence cytokine gene expression and cell death, while in myeloid leukemia cells its tyrosine phosphorylation is a key event in aberrant NF‑κB activation and survival signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in propagating receptor‐mediated signals, PRKD2 participates in the intracellular trafficking machinery. Early studies revealed that its C‑terminal regulatory domain binds diacylglycerol at the trans‐Golgi network and plays a critical part in vesicle formation and basolateral protein transport. PRKD2 also governs nucleocytoplasmic shuttling and recycling of membrane proteins—such as integrins in the context of Arf6–AMAP1 signaling—and modulates the secretion of hormones and immune mediators. Differential expression of PRKD2 in various epithelial and neuroendocrine tumor models underscores its importance in regulating both receptor turnover and secretory granule release, events essential for maintaining cellular homeostasis and proper tissue architecture."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPRKD2 further influences tumor progression by regulating cell migration, invasion, angiogenesis, and proliferation in diverse malignancies including pancreatic, glioblastoma, lung, prostate, and cervical cancers. Its activity not only enhances secretion of matrix metalloproteinases and growth factors but also modulates cell‐cycle progression via stabilization of Aurora A kinase. In addition, dimerization of PRKD2 is critical for its efficient control of actin reorganization and secretory pathways that underpin innate immune defenses. These multifaceted functions—as well as alterations such as PRKD2 gene rearrangements in salivary gland tumors and mutations associated with chemotherapy resistance—underscore the potential of PRKD2 as a novel therapeutic target in oncology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sabine Sturany, Johan Van Lint, Annette Gilchrist, et al. 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