{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProtein kinase C delta (PKCδ) acts as a critical mediator of cell stress responses and apoptosis. In various cell types, PKCδ is activated by pro‐apoptotic stimuli, undergoes specific tyrosine phosphorylations, and translocates to distinct intracellular compartments such as the nucleus, mitochondria, Golgi, or cytosol. These events enable PKCδ to phosphorylate key substrates including p53 (promoting Ser46 phosphorylation), p73, and Rad9, thereby triggering apoptotic cascades and amplifying ceramide‐mediated mitochondrial signals. In addition, PKCδ phosphorylates target proteins involved in membrane disassembly (e.g. lamin B1) and modulates the activity of apoptotic regulators in response to genotoxic stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn immune cells, PKCδ plays a pivotal role in innate host defense. It phosphorylates cytosolic components of the NADPH oxidase complex (for example, p47^phox), thereby promoting reactive oxygen species generation in neutrophils and monocytes. Moreover, in chronic lymphocytic leukemia (CLL) cells PKCδ is constitutively active downstream of phosphatidylinositol 3-kinase (PI3K), and its activity mediates survival signals that, when inhibited, promote apoptosis. PKCδ also regulates type I and type II interferon signaling by directly phosphorylating STAT proteins, further linking its activity to cytokine production, immunomodulation, and, in certain instances, dysregulated immunity as observed in autoimmune conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn epithelial and endothelial cells, PKCδ orchestrates inflammatory gene regulation and receptor transactivation. Its activation leads to the phosphorylation and nuclear activation of transcription factors such as NF-κB and drives the serine phosphorylation of Stat1, thereby facilitating interferon‐mediated gene expression. PKCδ modulates the expression of matrix metalloproteinases (e.g. MMP-9 and MMP-13) and adhesion molecules such as VCAM-1 by coordinating cross-talk between MAP kinases (including ERK, JNK, and p38) and transcription factors (such as AP-1, GATA, and NF-κB). In vascular and airway epithelia, PKCδ also contributes to VEGF-dependent Akt activation and to mucin secretion in response to injurious stimuli, highlighting its central role in regulating both proinflammatory signals and barrier function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in apoptosis, immunity, and inflammation, PKCδ is intimately involved in the regulation of oncogenic signals, cellular differentiation, and metabolic homeostasis. In various cancers, including prostate, cervical, and hepatocellular carcinomas, PKCδ modulates tumor suppressor pathways by phosphorylating transcription factors such as p53 and by regulating TP53 gene transcription, thereby influencing cell cycle arrest and cell death. It is also a downstream effector of viral oncoproteins (e.g. EBV’s LMP1) that trigger cascades involving EGFR, STAT3, and ERK. Furthermore, PKCδ has been implicated in the development of hepatic insulin resistance and is subject to regulation by microRNAs (for example, miR-181a), which alter its expression and impact radio-sensitivity. Additional studies demonstrate PKCδ-mediated cross-talk with kinases such as GSK-3 and its modulation by scaffolding proteins like RACK1/plectin, underscoring its broad influence on growth factor signaling, cardiomyocyte function, and even genetic disorders involving B-cell dysregulation and neurodegeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "26", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its functions in intracellular signaling cascades, PKCδ regulates platelet and vascular cell responses. In platelets, agonist-induced PKCδ activation is closely linked to dense granule secretion and thromboxane A₂ production, processes that are essential for platelet aggregation and hemostasis. This function further illustrates the versatile nature of PKCδ as an integrator of extracellular stimuli and intracellular effector mechanisms across diverse biological systems."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jian Ren, Rakesh Datta, Hisashi Shioya, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Human neutrophil elastase induces hypersecretion of mucin from well-differentiated human bronchial epithelial cells in vitro via a protein kinase C{delta}-mediated mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0002-9440(10)62040-8"}], "href": "https://doi.org/10.1016/s0002-9440(10"}, {"type": "t", "text": "62040-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16127146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16127146"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Stuart A Rushworth, Richard M Ogborne, Charles A Charalambos, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Regulation of lysophosphatidic acid-induced epidermal growth factor receptor transactivation and interleukin-8 secretion in human bronchial epithelial cells by protein kinase Cdelta, Lyn kinase, and matrix metalloproteinases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M511224200"}], "href": "https://doi.org/10.1074/jbc.M511224200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16687414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16687414"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Makoto Sumitomo, Motoi Ohba, Junichi Asakuma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase Cdelta amplifies ceramide formation via mitochondrial signaling in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI14146"}], "href": "https://doi.org/10.1172/JCI14146"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11901191"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11901191"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Constance E Runyan, H William Schnaper, Anne-Christine Poncelet "}, {"type": "b", "children": [{"type": "t", "text": "Smad3 and PKCdelta mediate TGF-beta1-induced collagen I expression in human mesangial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00082.2003"}], "href": "https://doi.org/10.1152/ajprenal.00082.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12759229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12759229"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Suman Kambhampati, Yongzhong Li, Amit Verma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of protein kinase C delta by all-trans-retinoic acid."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M301523200"}], "href": "https://doi.org/10.1074/jbc.M301523200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12805378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12805378"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Selma Osmanagic-Myers, Gerhard Wiche "}, {"type": "b", "children": [{"type": "t", "text": "Plectin-RACK1 (receptor for activated C kinase 1) scaffolding: a novel mechanism to regulate protein kinase C activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M312382200"}], "href": "https://doi.org/10.1074/jbc.M312382200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14966116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14966116"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Vitalyi O Rybin, Jianfen Guo, Abdelkarim Sabri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stimulus-specific differences in protein kinase C delta localization and activation mechanisms in cardiomyocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M311096200"}], "href": "https://doi.org/10.1074/jbc.M311096200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14970215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14970215"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Cyril H Benes, Ning Wu, Andrew E H Elia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The C2 domain of PKCdelta is a phosphotyrosine binding domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2005.02.019"}], "href": "https://doi.org/10.1016/j.cell.2005.02.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15851033"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15851033"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Q Wang, Y Zhou, X Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209004"}], "href": "https://doi.org/10.1038/sj.onc.1209004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16278684"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16278684"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Hee-Jeong Im, Prasuna Muddasani, Viswanathan Natarajan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Basic fibroblast growth factor stimulates matrix metalloproteinase-13 via the molecular cross-talk between the mitogen-activated protein kinases and protein kinase Cdelta pathways in human adult articular chondrocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M609040200"}], "href": "https://doi.org/10.1074/jbc.M609040200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17311929"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17311929"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Ugur Akar, Bulent Ozpolat, Kapil Mehta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue transglutaminase inhibits autophagy in pancreatic cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-06-0229"}], "href": "https://doi.org/10.1158/1541-7786.MCR-06-0229"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17374730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17374730"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Hanshao Liu, Zheng-Guang Lu, Yoshio Miki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase C delta induces transcription of the TP53 tumor suppressor gene by controlling death-promoting factor Btf in the apoptotic response to DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01126-07"}], "href": "https://doi.org/10.1128/MCB.01126-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17938203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17938203"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Anke Doller, Kai Schlepckow, Harald Schwalbe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tandem phosphorylation of serines 221 and 318 by protein kinase Cdelta coordinates mRNA binding and nucleocytoplasmic shuttling of HuR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01373-09"}], "href": "https://doi.org/10.1128/MCB.01373-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20086103"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20086103"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Misti C White, Rui Gao, Weidong Xu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PKCδ regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI46045"}], "href": "https://doi.org/10.1172/JCI46045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21576825"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21576825"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Elisabeth Salzer, Elisangela Santos-Valente, Stefanie Klaver, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-12-469544"}], "href": "https://doi.org/10.1182/blood-2012-12-469544"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23430113"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23430113"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Swaminathan Murugappan, Florin Tuluc, Robert T Dorsam, et al. 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