{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, PRKCA (protein kinase Cα) orchestrates diverse phosphorylation events that regulate key intracellular effectors. For example, in myotonic dystrophy type 1 models the inappropriate activation of PRKCA—working together with related isoforms—leads to the hyperphosphorylation and stabilization of RNA‐binding proteins such as CUGBP1, thereby contributing to disease pathogenesis. In addition, PRKCA directly phosphorylates cytosolic components of the NADPH oxidase complex in neutrophils to promote superoxide production, modulates endothelial nitric oxide synthase by altering its Ca²⁺ sensitivity and interactions with regulatory proteins, and uses a specialized C2 domain to target membranes and bind diacylglycerol and phospholipids that in turn influence diacylglycerol kinase activity and the stability of neuronal RNA regulators."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, PRKCA is a critical mediator of cell migration, adhesion and the epithelial–mesenchymal transition that underlie tumor progression. Its activity supports the acquisition of cancer stem cell features—for example, through the activation of transcriptional regulators like FRA1—and it modulates integrin‐dependent signaling as well as proteolytic processing of adhesion molecules (such as N-cadherin) that facilitate invasion. Moreover, aberrant PRKCA function influences both proliferative and apoptotic processes in diverse tumors including prostate, glioblastoma and lung cancers, with its messenger RNA often serving as a target for microRNAs that can suppress metastatic potential."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncogenesis, PRKCA plays pivotal roles in metabolic, vascular and immune signaling. It helps regulate lymphocyte activation by contributing to early phases of NF‑κB induction through T‑cell receptor signals, and it participates in innate antiviral and inflammatory pathways via interactions that involve histone deacetylase and β‑catenin. In endothelial cells and epithelial barriers, PRKCA governs tight junction integrity and modulates the endocytosis of key proteins such as nephrin, which is linked to glomerular permeability in diabetic nephropathy. Its kinase activity is also required for IGF‑mediated up‐regulation of COX‑2 expression, demonstrating a convergence of growth factor and inflammatory signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "31", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, altered PRKCA activity has been implicated in cardiovascular and neurological disorders. 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"}, {"type": "b", "children": [{"type": "t", "text": "Neuronal ELAV proteins enhance mRNA stability by a PKCalpha-dependent pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0504702102"}], "href": "https://doi.org/10.1073/pnas.0504702102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16099831"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16099831"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "John H Evans, Diana Murray, Christina C Leslie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific translocation of protein kinase Calpha to the plasma membrane requires both Ca2+ and PIP2 recognition by its C2 domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e05-06-0499"}], "href": "https://doi.org/10.1091/mbc.e05-06-0499"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16236797"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16236797"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Barbara A Klarl, Philipp A Lang, Daniela S Kempe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase C mediates erythrocyte \"programmed cell death\" following glucose depletion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00283.2005"}], "href": "https://doi.org/10.1152/ajpcell.00283.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16338977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16338977"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Itender Singh, Nebojsa Knezevic, Gias U Ahmmed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Galphaq-TRPC6-mediated Ca2+ entry induces RhoA activation and resultant endothelial cell shape change in response to thrombin."}]}, {"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.M608288200"}], "href": "https://doi.org/10.1074/jbc.M608288200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17197445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17197445"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "YoungHyun Shin, Sun-Hee Yoon, Eun-Young Choe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PMA-induced up-regulation of MMP-9 is regulated by a PKCalpha-NF-kappaB cascade in human lung epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emm.2007.11"}], "href": "https://doi.org/10.1038/emm.2007.11"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17334233"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17334233"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Irwan T Makagiansar, Scott Williams, Tomas Mustelin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential phosphorylation of NG2 proteoglycan by ERK and PKCalpha helps balance cell proliferation and migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200612084"}], "href": "https://doi.org/10.1083/jcb.200612084"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17591920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17591920"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "N Muge Kuyumcu-Martinez, Guey-Shin Wang, Thomas A Cooper "}, {"type": "b", "children": [{"type": "t", "text": "Increased steady-state levels of CUGBP1 in myotonic dystrophy 1 are due to PKC-mediated hyperphosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.07.027"}], "href": "https://doi.org/10.1016/j.molcel.2007.07.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17936705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17936705"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Hui Xu, Petra Czerwinski, Marcus Hortmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase C alpha promotes angiogenic activity of human endothelial cells via induction of vascular endothelial growth factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvm085"}], "href": "https://doi.org/10.1093/cvr/cvm085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18056764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18056764"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Chun-Hsien Chu, Bor-Show Tzang, Li-Mien Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Galphaq interaction and protein kinase C-alpha/CaMKII activation in H9c2 cardiomyoblast cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Endocrinol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1677/JOE-07-0619"}], "href": "https://doi.org/10.1677/JOE-07-0619"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18434368"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18434368"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Amanda E Bass-Zubek, Ryan P Hobbs, Evangeline V Amargo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200712133"}], "href": "https://doi.org/10.1083/jcb.200712133"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18474624"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18474624"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Alessio Paone, Donatella Starace, Roberta Galli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-alpha-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgn149"}], "href": "https://doi.org/10.1093/carcin/bgn149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18566014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18566014"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Chun-An Chen, Lawrence J Druhan, Saradhadevi Varadharaj, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of endothelial nitric-oxide synthase regulates superoxide generation from the enzyme."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M802269200"}], "href": "https://doi.org/10.1074/jbc.M802269200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18622039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18622039"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "L Ren, S H Hong, J Cassavaugh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The actin-cytoskeleton linker protein ezrin is regulated during osteosarcoma metastasis by PKC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2008.437"}], "href": "https://doi.org/10.1038/onc.2008.437"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19060919"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19060919"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Qi-Wen Fan, Christine Cheng, Zachary A Knight, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EGFR signals to mTOR through PKC and independently of Akt in glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.2000014"}], "href": "https://doi.org/10.1126/scisignal.2000014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19176518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19176518"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Zachary A Kohutek, Charles G diPierro, Gerard T Redpath, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADAM-10-mediated N-cadherin cleavage is protein kinase C-alpha dependent and promotes glioblastoma cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5126-08.2009"}], "href": "https://doi.org/10.1523/JNEUROSCI.5126-08.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19357285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19357285"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Nobuko Koshikawa, Jun-Ichi Hayashi, Akira Nakagawara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reactive oxygen species-generating mitochondrial DNA mutation up-regulates hypoxia-inducible factor-1alpha gene transcription via phosphatidylinositol 3-kinase-Akt/protein kinase C/histone deacetylase pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.054221"}], "href": "https://doi.org/10.1074/jbc.M109.054221"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19801684"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19801684"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Gry Kalstad Lønne, Louise Cornmark, Iris Omanovic Zahirovic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PKCalpha expression is a marker for breast cancer aggressiveness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-9-76"}], "href": "https://doi.org/10.1186/1476-4598-9-76"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20398285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20398285"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Xiao-Bo Zhou, Iris Wulfsen, Emine Utku, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dual role of protein kinase C on BK channel regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0912029107"}], "href": "https://doi.org/10.1073/pnas.0912029107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20385812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20385812"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Armen M Abramian, Eydith Comenencia-Ortiz, Mansi Vithlani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase C phosphorylation regulates membrane insertion of GABAA receptor subtypes that mediate tonic inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.149229"}], "href": "https://doi.org/10.1074/jbc.M110.149229"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20940303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20940303"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Ivo Quack, Magdalena Woznowski, Sebastian A Potthoff, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PKC alpha mediates beta-arrestin2-dependent nephrin endocytosis in hyperglycemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.204024"}], "href": "https://doi.org/10.1074/jbc.M110.204024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21321125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21321125"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Shilpi Arora, Aarati R Ranade, Nhan L Tran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-328 is associated with (non-small) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.25939"}], "href": "https://doi.org/10.1002/ijc.25939"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21448905"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21448905"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Wai Leong Tam, Haihui Lu, Joyce Buikhuisen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2013.08.005"}], "href": "https://doi.org/10.1016/j.ccr.2013.08.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24029232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24029232"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Chen Wang, Xueliang Wang, Hongwei Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-203 inhibits cell proliferation and migration of lung cancer cells by targeting PKCα."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0073985"}], "href": "https://doi.org/10.1371/journal.pone.0073985"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24040137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24040137"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Egeria Scoditti, Alessia Nestola, Marika Massaro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hydroxytyrosol suppresses MMP-9 and COX-2 activity and expression in activated human monocytes via PKCα and PKCβ1 inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2013.10.017"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2013.10.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24401212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24401212"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Feng Chen, Yanfang Yu, Steven Haigh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of NADPH oxidase 5 by protein kinase C isoforms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0088405"}], "href": "https://doi.org/10.1371/journal.pone.0088405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24505490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24505490"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Brock Humphries, Zhishan Wang, Aaron L Oom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-200b targets protein kinase Cα and suppresses triple-negative breast cancer metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgu133"}], "href": "https://doi.org/10.1093/carcin/bgu133"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24925028"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24925028"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Shigeru Shibata, Juan Pablo Arroyo, María Castañeda-Bueno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Angiotensin II signaling via protein kinase C phosphorylates Kelch-like 3, preventing WNK4 degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1418342111"}], "href": "https://doi.org/10.1073/pnas.1418342111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25313067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25313067"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Stephanie I Alfonso, Julia A Callender, Basavaraj Hooli, et al. 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