{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPRKCQ, which encodes protein kinase C‐θ (PKCθ), plays a central role in T lymphocyte signal transduction. Upon T cell receptor (TCR) triggering, PKCθ becomes activated—often via costimulatory pathways that are independent of classical phospholipase C–mediated diacylglycerol generation—and is selectively recruited to the immunological synapse where it orchestrates multiple downstream signaling events. This kinase facilitates activation of transcription factors such as NF‐κB, AP‐1, and NFAT, thereby promoting IL-2 production, T cell proliferation, and survival. In addition, PKCθ modulates early Ca²⁺ influx and participates in the formation of TCR–microclusters, processes that are fine-tuned by post-translational modifications including autophosphorylation and sumoylation. Moreover, PKCθ forms complexes with other signaling molecules (for example, via binding to RapGEF2 or associating with nuclear regulators and adaptor proteins like filamin A) and even has roles in noncanonical, nuclear, or mitochondrial signaling events that help shape both effector and regulatory T cell responses, as well as responses to interferons and viral proteins."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its critical functions in T cells, PKCθ has been implicated in diverse pathophysiological processes. Genetic association studies have identified variants at the PRKCQ locus as risk factors for rheumatoid arthritis and predictors of joint destruction, underscoring the kinase’s role in modulating autoimmune inflammation. In metabolic tissues, PKCθ activation contributes to lipid-induced insulin resistance in muscle. In platelets, PKCθ participates in receptor‐mediated secretion and aggregation through interactions with kinases such as Bruton's tyrosine kinase, impacting thrombus stability. Moreover, PKCθ is exploited as a diagnostic marker and potential therapeutic target in tumors such as gastrointestinal stromal tumors (GIST), and in certain contexts—such as in T cell acute lymphoblastic leukemia or in breast cancer—PKCθ signaling influences malignant cell survival, epithelial–mesenchymal transition, and invasive behavior. Altogether, the multifunctional actions of PKCθ connect T cell–driven immune responses with broader roles in inflammation, metabolism, hemostasis, and oncogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kelly-Ann Sheppard, Lori J Fitz, Julie M Lee, et al. 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