{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSerine/arginine protein kinase 2 (SRPK2) plays a pivotal role in regulating viral protein function during infection. In the context of hepatitis B virus (HBV) replication, SRPK2—as well as its close homolog SRPK1—phosphorylates the core protein’s arginine‐rich domain, a modification essential for pregenomic RNA encapsidation and proper capsid assembly. Similarly, SRPK2 phosphorylates the Epstein–Barr virus (EBV) tegument protein BLRF2, with its docking interactions being critical for efficient viral replication. Recent cryo-electron microscopy studies have further revealed that SRPK2 employs a conserved substrate-docking groove to regulate the phosphorylation status of viral proteins and to modulate the assembly process of viral capsids."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its critical role in viral replication, SRPK2 is an important regulator of host RNA processing and cell cycle progression. It associates with spliceosomal complexes by phosphorylating key splicing factors—such as PRP28 and various serine/arginine-rich (SR) proteins—thereby facilitating spliceosome assembly and pre-mRNA processing. In neurons, SRPK2 activation through Akt-mediated phosphorylation drives its nuclear translocation, which in turn upregulates cyclin D1 and triggers cell cycle reentry and apoptosis. SRPK2 also safeguards genomic stability by phosphorylating the DDX23 helicase, thus suppressing the formation of deleterious R-loops and DNA double-strand breaks. In oncogenesis, SRPK2 phosphorylates the splicing regulator acinus to enhance cyclin A1 expression, contributing to aberrant cell cycle progression and proliferation in leukemia. Moreover, its overexpression has been linked to enhanced cell growth, invasion, and chemoresistance in several cancers—including colon, prostate, pancreatic, and colorectal carcinomas—with pharmacological inhibition of SRPK2 resulting in significant cytotoxic effects in leukemia cells and reduced stress granule formation in obesity-associated pancreatic ductal adenocarcinoma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSRPK2 also exerts nuanced control over substrate specificity and cellular adaptations by modulating the phosphorylation profiles of splicing factors. Detailed kinetic and binding studies have highlighted that a conserved SRPK2 substrate-docking groove underlies its ability to selectively phosphorylate targets such as SRSF3, thereby influencing their subcellular localization and activity. Furthermore, SRPK2 regulates the self-assembly of presynaptic active zone proteins—an essential process for proper synaptic formation and neurotransmitter release. Its transcriptional upregulation following intensive aerobic exercise suggests a broader role in the cellular response to stress and adaptation through modulation of the splicing machinery."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Henrik Daub, Stephanie Blencke, Peter Habenberger, et al. 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