Affinage

PRKCB

Protein kinase C beta type · UniProt P05771

Length
671 aa
Mass
76.9 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRKCB (PKCβ) is a diacylglycerol/Ca2+-activated serine/threonine kinase that transduces receptor-proximal signals into transcriptional, cytoskeletal, metabolic, and chromatin outputs across immune, vascular, skeletal, and neuronal contexts (PMID:12118249, PMID:20228790, PMID:23599343). In B-cell receptor signaling it occupies a central node: it is required to recruit and activate the IKK complex in lipid rafts to drive NF-κB-dependent survival (PMID:12118249), acts upstream of CARMA1 phosphorylation and CARMA1/Bcl-10/MALT-1 assembly (PMID:26936881), and simultaneously imposes negative feedback by phosphorylating a conserved serine in the Btk Tec-homology linker to limit Btk membrane recruitment (PMID:11598012). Beyond signaling, PKCβI functions as a chromatin-modifying kinase, writing the histone mark H3T6ph to block LSD1-mediated demethylation of H3K4 and thereby sustain androgen-receptor- and EWSR1-FLI1-driven transcription (PMID:20228790, PMID:22930730). It controls transcription-factor activity and organelle programs downstream of RANKL by phosphorylating TFEB to drive lysosomal biogenesis for bone resorption (PMID:23599343) and by inactivating GSK-3β to induce NFATc1 during osteoclastogenesis (PMID:25256217). PKCβ further phosphorylates a broad substrate set to regulate vascular barrier integrity via occludin Ser490 (PMID:35576527), mitochondrial ROS and apoptosis via p66Shc (PMID:27624939), antiviral innate immunity by phosphorylating RIG-I at S8/T170 to suppress TRIM25-mediated ubiquitination and IFN induction (PMID:22114345), and ion-channel/transporter behavior including TRPM8 and PI3Kγ p110γ (PMID:32290846, PMID:23824069). Its spatial activity is constrained by scaffolds and regulators including RACK1, TRPC3, PICK1, and the lncRNA VEAL2, which target or tune the kinase at melanosomes, plasma membrane, and mitochondria (PMID:15252133, PMID:20179100, PMID:32048876, PMID:34180064).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Established that PKCβ is not only an activator of BCR signaling but also a built-in brake, defining how the pathway is self-limiting.

    Evidence PKCβ knockout mice plus site-directed mutagenesis of the Btk Tec-homology linker serine with Ca2+ and membrane-fractionation readouts

    PMID:11598012

    Open questions at the time
    • Did not resolve how PKCβ access to Btk is spatially or temporally gated
    • Did not connect this feedback to the parallel NF-κB-activating arm
  2. 2002 High

    Placed PKCβ genetically upstream of IKK in BCR survival signaling, answering where the kinase acts in NF-κB activation.

    Evidence PKCβ knockout B cells with lipid raft fractionation, IKK activity, and IκB degradation assays

    PMID:12118249

    Open questions at the time
    • Direct IKK or scaffold substrate of PKCβ not identified
    • Mechanism of IKK raft recruitment left unresolved
  3. 2006 High

    Showed scaffold-directed targeting confers substrate and isoform specificity, explaining how PKCβ but not PKCα acts on a given organelle target.

    Evidence Melanosome purification with reciprocal Co-IP, RACK1 siRNA, DECA disruption, and tyrosinase activity assays

    PMID:15252133

    Open questions at the time
    • Tyrosinase phosphosites not precisely mapped
    • Generality of RACK1-PKCβ targeting beyond melanosomes untested here
  4. 2010 High

    Redefined PKCβI as a chromatin-modifying enzyme, showing a kinase can write a histone mark that protects an adjacent methyl mark from erasure.

    Evidence In vitro LSD1 peptide demethylation assays, ChIP, RNAi with rescue, in vitro kinase assay, and tumor xenograft

    PMID:20228790

    Open questions at the time
    • How PRK1-primed PKCβI is recruited to specific AR promoters not fully resolved
    • Genome-wide scope of H3T6ph not defined
  5. 2010 High

    Demonstrated TRPC3 acts as both Ca2+ channel and direct scaffold, coupling DAG/Ca2+ signals to sustained PKCβ membrane residence.

    Evidence TRPC3-deficient DT40 B cells with electrophysiology, translocation imaging, Co-IP, and ERK readouts

    PMID:20179100

    Open questions at the time
    • Structural basis of the TRPC3-PKCβ interaction unknown
    • Whether scaffold dictates substrate choice not addressed
  6. 2011 High

    Identified PKCα/β as constitutive negative regulators of antiviral IFN signaling through direct RIG-I phosphorylation.

    Evidence Co-IP, RIG-I S8/T170 mutagenesis, gene silencing, inhibitor treatment, IFN induction and VSV resistance assays

    PMID:22114345

    Open questions at the time
    • How infection relieves PKCβ-mediated suppression not defined
    • Relative contributions of PKCα versus PKCβ not separated
  7. 2013 High

    Connected RANKL signaling to organelle biogenesis by mapping PKCβ phosphorylation of TFEB to lysosome-dependent bone resorption.

    Evidence Cell-based phosphorylation mapping of TFEB C-terminal serines, osteoclast-specific KO mice, lysosomal gene readouts

    PMID:23599343

    Open questions at the time
    • How phosphorylation stabilizes TFEB mechanistically not fully resolved
    • Crosstalk with other TFEB kinases not addressed
  8. 2013 High

    Extended PKCβ substrate scope to lipid kinase regulation, showing it can rewire PI3Kγ away from its canonical GPCR inputs.

    Evidence In vitro kinase assay, phospho-mimetic mutagenesis, Co-IP, HDX-MS, and PKCβ knockout cells

    PMID:23824069

    Open questions at the time
    • In vivo consequences of p110γ Ser582 phosphorylation not established
    • Effect on PI3Kγ output magnitude beyond p84 release unquantified
  9. 2016 Medium

    Revised the p66Shc phosphosite assignment, refining how PKCβ controls mitochondrial ROS and apoptosis.

    Evidence In vitro kinase assay, mutagenesis of p66Shc Ser139/Ser213, ROS and cell-death readouts, PKCβ knockout cells

    PMID:27624939

    Open questions at the time
    • Contradicts prior Ser36 model and not independently confirmed
    • Upstream activation of PKCβ in this cascade not detailed
  10. 2022 High

    Defined a specific occludin phosphosite (S490) through which PKCβ governs vascular permeability and hemorrhagic risk.

    Evidence MCAO model in tPA-/- mice, S490A occludin knock-in, PKCβ inhibition, permeability and hemorrhage readouts

    PMID:35576527

    Open questions at the time
    • How tPA activates PKCβ upstream not mechanistically mapped
    • Whether other junctional substrates contribute not addressed
  11. 2021 Medium

    Showed PKCβ2 activity is tuned by a noncoding RNA competing with its lipid activator, adding an RNA-level layer of kinase regulation.

    Evidence VEAL2 pulldown with PRKCB2 bait, kinase activity assays, zebrafish veal2 KO, HUVEC permeability and rescue experiments

    PMID:34180064

    Open questions at the time
    • Structural basis of VEAL2-DAG competition not resolved
    • Generality across PKCβ-dependent tissues untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single kinase achieves substrate, isoform, and subcellular selectivity across chromatin, mitochondria, plasma membrane, and organelles remains the central unresolved question.
  • No unified model linking spatial targeting to substrate choice
  • Isoform-specific (βI vs βII) functional partitioning incompletely defined
  • Structural basis of most substrate recognitions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 5 GO:0042393 histone binding 2
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 2 GO:0005739 mitochondrion 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 2 R-HSA-9612973 Autophagy 1
Partners
BTKPICK1PKD1RACK1RBCK1RIG-ITRPC3

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 PKCβ is specifically required for BCR-mediated NF-κB activation; PKCβ-deficient B cells fail to recruit the IKK complex into lipid rafts, activate IKK, or degrade IκB, placing PKCβ upstream of IKK in the BCR survival signaling pathway. PKCβ knockout mice, lipid raft fractionation, IKK activity assays, IκB degradation assays Nature immunology High 12118249
2001 PKCβ acts as a feedback inhibitor of Btk activation by phosphorylating a conserved serine in the Tec homology domain linker of Btk; mutation of this site enhances Btk tyrosine phosphorylation, membrane association, and augmented BCR/FcεRI-mediated signaling. PKCβ knockout mice, site-directed mutagenesis of Btk phosphorylation site, Ca2+ signaling assays, membrane fractionation The EMBO journal High 11598012
2010 PKCβI phosphorylates histone H3 at threonine 6 (H3T6ph) during androgen receptor (AR)-dependent gene activation, preventing LSD1 from demethylating H3K4 (but not H3K9), thereby writing a new chromatin mark that maintains active methylation states. PKCβI is recruited to AR target gene promoters after androgen stimulation, requiring prior activation by the gatekeeper kinase PRK1. In vitro histone peptide LSD1 demethylation assays, ChIP, RNAi knockdown, in vivo tumor xenograft, in vitro kinase assay Nature High 20228790
2013 In differentiated osteoclasts, RANKL activates PKCβ, which phosphorylates the transcription factor TFEB on three serine residues in its C-terminal 15 amino acids, stabilizing and activating TFEB to promote lysosomal biogenesis necessary for bone resorption. Cell-based phosphorylation assays, osteoclast-specific gene deletion in mice, cell size/lysosomal gene expression assays, Western blot Genes & development High 23599343
2013 PKCβ phosphorylates Ser582 in the helical domain of the PI3Kγ catalytic subunit p110γ in response to FcεRI clustering and/or store-operated Ca2+ influx in mast cells, correlating with release of the p84 adapter subunit from the p84-p110γ complex and increased p110γ activity, thereby disconnecting PI3Kγ from its canonical GPCR inputs. In vitro kinase assay, phospho-mimicking mutagenesis, Co-IP, hydrogen-deuterium exchange mass spectrometry, PKCβ knockout cells PLoS biology High 23824069
2006 RACK1 anchors activated PKCβ specifically on melanosome membranes, allowing PKCβ (but not PKCα) to phosphorylate tyrosinase on specific serine residues on its cytoplasmic domain, activating melanogenesis. Disruption of RACK1-PKCβ interaction with DECA or siRNA knockdown of RACK1 decreases tyrosinase activity. Melanosome purification, co-immunoprecipitation, siRNA knockdown of RACK1, tyrosinase activity assays, DECA pharmacological disruption Journal of cell science High 15252133
2010 In B cells, TRPC3 serves as both a Ca2+-permeable channel and a direct protein scaffold for PKCβ at the plasma membrane; TRPC3 deficiency impairs DAG-activated Ca2+ currents and the sustained BCR-stimulated translocation of PKCβ to the plasma membrane, preventing downstream ERK activation. TRPC3-deficient DT40 B cells, electrophysiology, PKCβ translocation imaging, Co-IP (direct PKCβ-TRPC3 association), ERK activation assays Journal of cell science High 20179100
2011 PKCα and PKCβ phosphorylate RIG-I at S8 and T170, suppressing TRIM25 binding and K63-linked ubiquitination of RIG-I, thereby negatively regulating RIG-I antiviral IFN signaling under normal conditions. PKCα/β interact with RIG-I under normal (unstimulated) conditions. Co-immunoprecipitation, site-directed mutagenesis of RIG-I S8/T170, gene silencing, pharmacological inhibition, IFN induction assays, VSV infection resistance assays Journal of virology High 22114345
2022 tPA activates PKCβ, which phosphorylates occludin at serine 490 (S490) in the ischemic penumbra, increasing cerebrovascular permeability and the risk of hemorrhagic transformation. Blocking S490 phosphorylation with a non-phosphorylatable occludin (S490A) or PKCβ inhibition reduces permeability and intracerebral hemorrhage. Mouse MCAO model (tPA-/- mice), intraventricular tPA injection, S490A occludin knock-in, PKCβ pharmacological inhibition, permeability assays, Western blot Blood High 35576527
2010 H2O2 activates a PKCβ/p66Shc/NF-κB signaling cascade in osteoblastic cells; p66Shc is an essential mediator of H2O2-induced apoptosis and NF-κB activation downstream of PKCβ. Estrogens and androgens attenuate these effects by suppressing PKCβ phosphorylation via a non-nuclear (membrane-initiated) mechanism. H2O2 treatment of mesenchymal/osteoblastic cell models, siRNA knockdown of p66Shc, polymeric estradiol (non-nuclear ER action), Western blot, apoptosis assays Molecular endocrinology Medium 20685851
2012 PRKCB (PKCβ) phosphorylates histone H3T6 to globally maintain H3K4 trimethylation at gene promoters in Ewing sarcoma cells; transcriptional activation of PRKCB is directly regulated by the EWSR1-FLI1 chimeric oncogene. PRKCB loss induces apoptosis in vitro and prevents tumor growth in vivo. Gene expression profiling, ChIP for H3T6ph/H3K4me3, siRNA/shRNA knockdown of PRKCB, in vivo xenograft models Cancer research Medium 22930730
2010 PKCβ activates HuR (ELAV protein) via phosphorylation in the diabetic retina, increasing HuR binding to VEGF mRNA and stabilizing it, leading to enhanced VEGF protein expression. PKCβ inhibition blocks this PKCβ/HuR/VEGF pathway. Streptozotocin diabetic rat model, immunoprecipitation/RT-PCR (RNP complexes), PKCβ inhibitor treatment, Western blot for HuR phosphorylation Biochemical pharmacology Medium 20599775
2012 PKCβ activation induced by diabetes decreases GLP-1 receptor (GLP-1R) expression in glomerular endothelial cells by increasing its ubiquitination-dependent degradation and enhancing phospho-c-Raf(Ser338)/ERK1/2 activation by angiotensin II. EC-PKCβ2 transgenic mice, siRNA knockdown of GLP-1R, Western blot, ubiquitination assays Diabetes Medium 22826029
2013 PKCβ activates the RhoA/Rho-kinase/MLC2 pathway in brain microvascular endothelial cells exposed to high glucose, leading to decreased occludin expression, cytoskeletal changes, and blood-brain barrier dysfunction. siRNA knockdown of PKCβ, PKCβ inhibitor (LY333531), transendothelial electrical resistance, FITC-dextran permeability, Rho activity assays, Western blot Journal of cerebral blood flow and metabolism Medium 23963366
2004 PKCβ activation in osteoblastic cells mediates PTH-, TNF-α-, and IL-1β-stimulated IL-6 promoter activation and PTH-stimulated bone resorption; PTH/TNF-α/IL-1β induces translocation of PKCβI (but not PKCα) to the plasma membrane, and this translocation is blocked by a selective PKCβ antagonist (LY379196). PKCβ translocation assays, IL-6 promoter-luciferase reporter, selective PKCβ inhibitor (LY379196), fetal rat bone organ culture resorption assay Experimental cell research Medium 11478844
2017 PKCβ-dependent activation of FAK is required for B cell mechanosensing; PMA-induced PKCβ activation can bypass Btk and PLCγ2 to activate FAK, which potentiates B cell spreading and adhesion. FAK inactivation or deficiency impairs B cell discrimination of substrate stiffness. PKCβ pharmacological activation (PMA), FAK inhibitor/KO, B cell spreading assays on substrates of varying stiffness, signaling Western blots eLife Medium 28755662
2006 RBCK1 binds PKCβI and is a key regulator of PKCβI function in cardiac myocytes; RBCK1 overexpression induces cardiac cell hypertrophy in a PKCβ-dependent manner, and RNAi of RBCK1 inhibits phenylephrine-induced hypertrophy. RBCK1 association with PKCβI increases transiently upon phenylephrine stimulation. Co-immunoprecipitation, adenoviral RBCK1 overexpression, siRNA knockdown of RBCK1, PKCβ-selective antagonist treatment, cardiomyocyte cell size measurements The Journal of biological chemistry Medium 17121852
1999 PKCβ mediates PMA-dependent stimulation of Na+,K+-ATPase in proximal tubule cells, while PKCζ mediates dopamine-dependent inhibition; these two isoforms exert opposing effects on Na+,K+-ATPase activity, as demonstrated with isoform-specific inhibitor peptides and LY333531. Isoform-specific PKC inhibitor peptides, LY333531 (PKCβ inhibitor), Na+,K+-ATPase activity assays FEBS letters Medium 10452527
2013 PRKCB (PKCβ) activation negatively modulates mitochondrial membrane potential and inhibits autophagy; pharmacological PRKCB inhibition and PRKCB knockout MEFs show increased autophagy and increased mitochondrial membrane potential, placing PRKCB upstream of mitochondrial energy status in the regulation of autophagy. PKCβ pharmacological inhibitor, prkcb knockout MEFs, autophagy flux assays, mitochondrial membrane potential measurements Autophagy Medium 23778835
2016 PKCβ mediates MIF-induced IL-8 production in bone marrow mesenchymal stromal cells via MIF receptor CD74; this IL-8 supports AML blast survival, placing PKCβ in a MIF→CD74→PKCβ→IL-8 stromal signaling axis. Recombinant MIF treatment, MIF inhibitor (ISO-1), PKCβ inhibitor, co-culture assays, cytokine ELISA Cancer research Medium 27872094
2008 PKCβ contributes to lung ischemia/reperfusion injury by coordinated activation of ERK1/2 and JNK MAPKs and induction of Egr-1 (early growth response-1) and its downstream target genes, particularly in mononuclear phagocytes; PKCβ null mice and ruboxistaurin treatment reduce these responses and improve survival. PKCβ knockout mice, ruboxistaurin pharmacological inhibition, murine single-lung I/R model, MAPK phosphorylation Western blots, Egr-1 expression assays The Journal of clinical investigation Medium 15173888
2008 PKCβII mediates myocardial ischemia/reperfusion injury at least in part via JNK phosphorylation and caspase-3 activation; PKCβ null mice and ruboxistaurin treatment show decreased infarct size, improved LV function, and reduced JNK phosphorylation/caspase-3 activation. PKCβ knockout mice, ruboxistaurin treatment, coronary artery occlusion/reperfusion model, JNK/caspase-3 Western blots, infarct size measurement American journal of physiology. Heart and circulatory physiology Medium 18245560
2005 PKCβ is required for neointimal expansion after acute arterial injury; PKCβII regulates vascular smooth muscle cell migration and proliferation, at least in part via ERK1/2 MAPK and Egr-1 transcription factor activation. PKCβ knockout mice, ruboxistaurin treatment, femoral artery denudation injury model, ERK1/2 and Egr-1 expression assays, in vitro SMC assays Circulation research Medium 15662033
2008 PKCβII activation in aortic endothelial cells is a critical upstream regulator of Egr-1 and MMP-2 in response to oxLDL via a PKCβ-JNK MAPK pathway; loss of PKCβ in apoE-/- mice reduces atherosclerotic lesion area with concomitant reductions in Egr-1 and MMP-2. PKCβ/apoE double-KO mice, ruboxistaurin pharmacological inhibition, primary endothelial cell PKCβ/JNK inhibitor experiments, MMP-2 activity assays, lesion quantification FASEB journal Medium 19036858
2015 PKCβ activation in diabetes reduces IL-18BP expression in endothelial cells, leading to unrestrained IL-18 signaling, VCAM-1 upregulation, and increased monocyte adhesion; siRNA, ruboxistaurin, and IL-18 neutralizing antibody each prevent elevated VCAM-1 and monocyte adherence. ApoE-/- diabetic mouse model with ruboxistaurin, siRNA knockdown of PKCβ/GLP-1R, EC/macrophage high-glucose treatment, monocyte adhesion assays, VCAM-1 Western blot Cardiovascular research Medium 25808972
2016 Usp9X is required for induction of PKCβ kinase activity after BCR-dependent activation in B lymphocytes; in Usp9X knockout B cells, PKCβ activity is reduced, leading to decreased CARMA1 phosphorylation, reduced CARMA1/Bcl-10/MALT-1 complex formation, and impaired NF-κB-dependent cell survival. Usp9X conditional knockout mice, BCR stimulation, CARMA1 phosphorylation/complex assays, NF-κB reporter, B cell survival assays Journal of immunology Medium 26936881
2015 PKCβ specifically interacts with and activates PKD1 in GPCR-stimulated neutrophils; PKCβ-PKD1 interaction and signaling are required for GPCR-mediated phosphorylation of the cofilin phosphatase SSH2, actin cytoskeletal reorganization, and neutrophil chemotaxis. Co-IP of PKCβ-PKD1, siRNA knockdown, pharmacological inhibition, neutrophil chemotaxis assays, cofilin phosphorylation assays Molecular biology of the cell Medium 25568344
2011 PKCβ phosphorylates glycine transporter 1 (GlyT1) on serine/threonine residues (not tyrosine); while classical PKCα/β regulate GlyT1 uptake, PKCβ-specific inhibitors selectively block GlyT1 phosphorylation without affecting glycine uptake, suggesting distinct roles for PKCα versus PKCβ in GlyT1 regulation. [32P]-orthophosphate metabolic labeling, isoform-selective PKC inhibitors (Gö6976, LY333531), glycine uptake assays in stably-transfected cells Neurochemistry international Medium 21864610
2001 Conditional expression of PKCβ in cardiac myocytes increases peak Ca2+ transient amplitude, extent and rate of shortening, and rate of relengthening, without altering phospholamban phosphorylation or SR Ca2+ uptake rates; at 10 months, maximum tension is depressed with increased myofilament protein phosphorylation. Transgenic mouse model with conditional PKCβ expression, Ca2+ transient measurements, sarcomere shortening assays, SR vesicle Ca2+-uptake assays, skinned fiber mechanics, Western blot American journal of physiology. Cell physiology Medium 11287324
2016 PKCβ-mediated phosphorylation of p66Shc occurs at Ser139 and Ser213 (not Ser36 as previously proposed), regulating p66Shc pro-oxidant and pro-apoptotic function; phosphomimetic mutation of Thr206 and Ser213 produces gain-of-function with increased ROS and cell death. In vitro kinase assay, site-directed mutagenesis of p66Shc phosphorylation sites, ROS measurements, cell death assays, PKCβ knockout cells The Journal of biological chemistry Medium 27624939
2002 PKCβ activation mediates HNE (4-hydroxynonenal)-induced MCP-1 release from murine macrophages, a distinct mechanism from LPS-induced MCP-1 secretion (which involves PKCδ). PKC isoform activity assays, pharmacological PKC inhibitors, MCP-1 ELISA in macrophages Biochemical and biophysical research communications Low 12056801
2008 Listeria monocytogenes PI-PLC promotes escape from the macrophage phagosome by generating diacylglycerol that activates host PKCβ; in PKCβ knockout macrophages, Listeria uses a PC-PLC-dependent (PKCβ-independent) pathway instead, demonstrating that PI-PLC-facilitated escape specifically requires host PKCβ. PKCβ knockout bone marrow-derived macrophages, bacterial escape assays, PI-PLC and PC-PLC mutant Listeria strains Microbial pathogenesis Medium 18996181
2002 Stress-induced AChE-R splice variant interacts intraneuronally with the scaffold protein RACK1, and through RACK1, with PKCβII in stress-responsive brain regions; elevated AChE-R is associated with increased RACK1/PKCβII co-localization and prolonged fear-induced behavioral inhibition. Co-immunoprecipitation of RACK1-PKCβII, antisense prevention of AChE-R, transgenic mice overexpressing AChE-R, immunohistochemistry, open-field behavioral testing Proceedings of the National Academy of Sciences Medium 12509514
1999 Glycated albumin (Amadori-modified) activates PKCβ (specifically PKCβ1 membrane translocation) in glomerular mesangial cells under physiological glucose concentrations, and this PKCβ activation is causally linked to increased collagen type IV production, as demonstrated by beta-specific PKC inhibitors. PKCβ-specific inhibitor (LY-379196), PKCβ1 membrane fractionation, PKC activity assay, collagen IV production assay The American journal of physiology Medium 10330050
2020 Chronic morphine activates MOR-PLC-PKCβ signaling, which phosphorylates TRPM8 at consensus PKC sites S1040 and S1041; this reduces TRPM8 desensitization and promotes TRPM8 hyperexcitability and cold hyperalgesia. Site-directed mutation of S1040/S1041 prevents MOR-induced TRPM8 desensitization reduction. Site-directed mutagenesis of TRPM8 S1040/S1041, PKCβ pharmacological inhibition, DRG neuronal electrophysiology, cold hyperalgesia behavioral assays in mice Molecular brain Medium 32290846
2014 PKCβ positively regulates RANKL-induced osteoclastogenesis by phosphorylating and inactivating GSK-3β, leading to NFATc1 induction. PKCβ expression increases in response to RANKL, and pharmacological or siRNA inhibition of PKCβ suppresses GSK-3β phosphorylation, NFATc1, and osteoclast differentiation. PKCβ pharmacological inhibition, siRNA knockdown, GSK-3β phosphorylation Western blot, NFATc1 induction assays, RANKL-injected mouse calvaria model Molecules and cells Medium 25256217
2004 PKCβ mediates serine phosphorylation of IRS-1 in adipocytes; overexpression of PKCβ induces IRS-1 mobility shift and serine phosphorylation and decreases insulin-stimulated glucose uptake, while dominant-negative PKCβ blocks these effects and enhances glucose uptake. In vitro PKC phosphorylation of immunoprecipitated IRS-1, PKCβ overexpression and dominant-negative PKCβ in adipocytes, 2-DOG uptake assays, Western blot Endocrine research Medium 15473137
2020 PKCβ mediates pulmonary vasoconstriction through interaction with the scaffolding protein PICK1 at mitochondria; PKCβ acutely translocates to mitochondria upon stimulation and activates mitoKATP channels, leading to mitochondrial ROS generation that drives vasoconstriction and pulmonary hypertension after intermittent hypoxia. Subcellular fractionation, proximity ligation assay (PKCβ-PICK1), mitoKATP inhibitors, antioxidant/PKCβ inhibitor in vivo, PKCβ inhibitor LY-333531, pulmonary artery contractility assays American journal of respiratory cell and molecular biology Medium 32048876
2021 lncRNA VEAL2 competes with diacylglycerol for binding to PRKCB2 and regulates its kinase activity; VEAL2 overexpression and knockdown modulate endothelial tubulogenesis and permeability, and VEAL2 can rescue PRKCB2-mediated turnover of junctional proteins. VEAL2 pulldown using PRKCB2 as bait, zebrafish veal2 knockout (cranial hemorrhage), HUVEC overexpression/knockdown, kinase activity assays, hyperglycemic HUVEC model The EMBO journal Medium 34180064

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 PKC-beta controls I kappa B kinase lipid raft recruitment and activation in response to BCR signaling. Nature immunology 264 12118249
2010 Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation at histone H3K4. Nature 244 20228790
2012 Protective effects of GLP-1 on glomerular endothelium and its inhibition by PKCβ activation in diabetes. Diabetes 182 22826029
2013 A RANKL-PKCβ-TFEB signaling cascade is necessary for lysosomal biogenesis in osteoclasts. Genes & development 162 23599343
1998 Inhibition of intraocular neovascularization caused by retinal ischemia in pigs by PKCbeta inhibition with LY333531. Investigative ophthalmology & visual science 130 9430559
2001 PKCbeta modulates antigen receptor signaling via regulation of Btk membrane localization. The EMBO journal 125 11598012
2010 Oxidative stress stimulates apoptosis and activates NF-kappaB in osteoblastic cells via a PKCbeta/p66shc signaling cascade: counter regulation by estrogens or androgens. Molecular endocrinology (Baltimore, Md.) 120 20685851
2006 PKCbeta-dependent activation of RhoA by syndecan-4 during focal adhesion formation. Journal of cell science 110 16787950
2010 The PKCbeta/HuR/VEGF pathway in diabetic retinopathy. Biochemical pharmacology 103 20599775
2012 IL-17 contributes to cardiac fibrosis following experimental autoimmune myocarditis by a PKCβ/Erk1/2/NF-κB-dependent signaling pathway. International immunology 102 22531062
2005 Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 102 15920548
2002 Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCbeta II correlates with intensified fear-induced conflict behavior. Proceedings of the National Academy of Sciences of the United States of America 102 12509514
2011 Conventional protein kinase C-α (PKC-α) and PKC-β negatively regulate RIG-I antiviral signal transduction. Journal of virology 99 22114345
2003 Acyclic N-(azacycloalkyl)bisindolylmaleimides: isozyme selective inhibitors of PKCbeta. Bioorganic & medicinal chemistry letters 86 12749884
1999 PKC-beta and PKC-zeta mediate opposing effects on proximal tubule Na+,K+-ATPase activity. FEBS letters 83 10452527
2013 PRKCB/protein kinase C, beta and the mitochondrial axis as key regulators of autophagy. Autophagy 81 23778835
2016 MIF-Induced Stromal PKCβ/IL8 Is Essential in Human Acute Myeloid Leukemia. Cancer research 79 27872094
2009 PKCbeta is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKCbeta as a therapeutic target in chronic lymphocytic leukemia. Blood 72 19168795
2000 PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats. Investigative ophthalmology & visual science 71 10937586
2015 PKC-β activation inhibits IL-18-binding protein causing endothelial dysfunction and diabetic atherosclerosis. Cardiovascular research 70 25808972
2012 PKCβ inhibition with ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes. Clinical science (London, England : 1979) 69 21892921
2008 Mice deficient in PKCbeta and apolipoprotein E display decreased atherosclerosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 66 19036858
2013 PKCβ promotes vascular inflammation and acceleration of atherosclerosis in diabetic ApoE null mice. Arteriosclerosis, thrombosis, and vascular biology 61 23766264
2010 Follow-up study identifies two novel susceptibility loci PRKCB and 8p11.21 for systemic lupus erythematosus. Rheumatology (Oxford, England) 60 21134959
2020 Curcumin reverses diabetic nephropathy in streptozotocin-induced diabetes in rats by inhibition of PKCβ/p66Shc axis and activation of FOXO-3a. The Journal of nutritional biochemistry 59 33017608
2010 Ca2+ influx and protein scaffolding via TRPC3 sustain PKCbeta and ERK activation in B cells. Journal of cell science 59 20179100
2012 Targeting the EWSR1-FLI1 oncogene-induced protein kinase PKC-β abolishes ewing sarcoma growth. Cancer research 56 22930730
2005 Haplotypes in the gene encoding protein kinase c-beta (PRKCB1) on chromosome 16 are associated with autism. Molecular psychiatry 56 16027742
2004 PKCbeta regulates ischemia/reperfusion injury in the lung. The Journal of clinical investigation 55 15173888
2013 PKC-β exacerbates in vitro brain barrier damage in hyperglycemic settings via regulation of RhoA/Rho-kinase/MLC2 pathway. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 54 23963366
2017 Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase. eLife 53 28755662
2001 Increased contractility and altered Ca(2+) transients of mouse heart myocytes conditionally expressing PKCbeta. American journal of physiology. Cell physiology 51 11287324
2022 Thrombolytic tPA-induced hemorrhagic transformation of ischemic stroke is mediated by PKCβ phosphorylation of occludin. Blood 48 35576527
2016 A novel missense variant in PRKCB segregates low-frequency hearing loss in an autosomal dominant family with Meniere's disease. Human molecular genetics 48 27329761
2001 PKC-beta is not necessary for cardiac hypertrophy. American journal of physiology. Heart and circulatory physiology 48 11299230
2014 PKC-β as a therapeutic target in CLL: PKC inhibitor AEB071 demonstrates preclinical activity in CLL. Blood 46 25001469
2002 Activation of PKC-beta isoforms mediates HNE-induced MCP-1 release by macrophages. Biochemical and biophysical research communications 46 12056801
2021 LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy. The EMBO journal 45 34180064
2009 Comprehending the complex connection between PKCbeta, TAK1, and IKK in BCR signaling. Immunological reviews 45 19909372
2008 PKCbeta modulates ischemia-reperfusion injury in the heart. American journal of physiology. Heart and circulatory physiology 44 18245560
1999 Glycated albumin stimulation of PKC-beta activity is linked to increased collagen IV in mesangial cells. The American journal of physiology 43 10330050
2015 GPCR-mediated PLCβγ/PKCβ/PKD signaling pathway regulates the cofilin phosphatase slingshot 2 in neutrophil chemotaxis. Molecular biology of the cell 42 25568344
2014 Increased extracellular pressure stimulates tumor proliferation by a mechanosensitive calcium channel and PKC-β. Molecular oncology 41 25454347
2008 Epstein-Barr virus latent membrane protein 1 mediates serine 25 phosphorylation and nuclear entry of annexin A2 via PI-PLC-PKCalpha/PKCbeta pathway. Molecular carcinogenesis 41 18412141
2013 PKCβ phosphorylates PI3Kγ to activate it and release it from GPCR control. PLoS biology 40 23824069
2009 Ruboxistaurin: PKC-beta inhibition for complications of diabetes. Expert opinion on pharmacotherapy 40 19929710
2016 Usp9X Is Required for Lymphocyte Activation and Homeostasis through Its Control of ZAP70 Ubiquitination and PKCβ Kinase Activity. Journal of immunology (Baltimore, Md. : 1950) 39 26936881
2010 Blockade of PKC-beta protects HUVEC from advanced glycation end products induced inflammation. International immunopharmacology 37 20875828
2006 Clinical safety of the selective PKC-beta inhibitor, ruboxistaurin. Expert opinion on drug safety 37 17044810
2010 A PKC-beta inhibitor protects against cardiac microvascular ischemia reperfusion injury in diabetic rats. Apoptosis : an international journal on programmed cell death 35 20044781
2010 A PKC-beta inhibitor treatment reverses cardiac microvascular barrier dysfunction in diabetic rats. Microvascular research 35 20079359
2004 The receptor for activated C-kinase-I (RACK-I) anchors activated PKC-beta on melanosomes. Journal of cell science 35 15252133
2019 hsa_circ_0092306 Targeting miR-197-3p Promotes Gastric Cancer Development by Regulating PRKCB in MKN-45 Cells. Molecular therapy. Nucleic acids 34 31689616
2014 Up-regulated HMGB1 in EAM directly led to collagen deposition by a PKCβ/Erk1/2-dependent pathway: cardiac fibroblast/myofibroblast might be another source of HMGB1. Journal of cellular and molecular medicine 32 24912759
2016 PKCβ Inhibitors Attenuate Amphetamine-Stimulated Dopamine Efflux. ACS chemical neuroscience 30 26996926
2014 Blockade of PKCβ protects against remote organ injury induced by intestinal ischemia and reperfusion via a p66shc-mediated mitochondrial apoptotic pathway. Apoptosis : an international journal on programmed cell death 30 24930012
1994 Expression of protein kinase C isozymes in guinea pig epidermis: selective inhibition of PKC-beta activity by 13-hydroxyoctadecadienoic acid-containing diacylglycerol. Journal of lipid research 30 8071613
2008 The ability of Listeria monocytogenes PI-PLC to facilitate escape from the macrophage phagosome is dependent on host PKCbeta. Microbial pathogenesis 29 18996181
2001 A PKCbeta isoform mediates phorbol ester-induced activation of Erk1/2 and expression of neuronal differentiation genes in neuroblastoma cells. FEBS letters 29 11707282
2020 circ-PRKCB acts as a ceRNA to regulate p66Shc-mediated oxidative stress in intestinal ischemia/reperfusion. Theranostics 28 32929374
2001 Involvement of PKC-beta in PTH, TNF-alpha, and IL-1 beta effects on IL-6 promoter in osteoblastic cells and on PTH-stimulated bone resorption. Experimental cell research 28 11478844
2013 Role of PKC-β in chemical allergen-induced CD86 expression and IL-8 release in THP-1 cells. Archives of toxicology 27 24136171
2003 Identification of a common risk haplotype for diabetic nephropathy at the protein kinase C-beta1 (PRKCB1) gene locus. Journal of the American Society of Nephrology : JASN 27 12874455
2020 Intermittent Hypoxia Augments Pulmonary Vasoconstrictor Reactivity through PKCβ/Mitochondrial Oxidant Signaling. American journal of respiratory cell and molecular biology 26 32048876
1999 Effect of tumor necrosis factor-alpha on insulin signal transduction in rat adipocytes: relation to PKCbeta and zeta translocation. Biochimica et biophysica acta 26 10209302
2014 Reversible blockade of complex I or inhibition of PKCβ reduces activation and mitochondria translocation of p66Shc to preserve cardiac function after ischemia. PloS one 25 25436907
2009 Ruboxistaurin, a PKCbeta inhibitor, inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt. Experimental eye research 25 19825373
2009 Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-β. The pharmacogenomics journal 25 20029385
2017 ELAC (3,12-di-O-acetyl-8-O-tigloilingol), a plant-derived lathyrane diterpene, induces subventricular zone neural progenitor cell proliferation through PKCβ activation. British journal of pharmacology 24 28476069
2016 Novel Insights into the PKCβ-dependent Regulation of the Oxidoreductase p66Shc. The Journal of biological chemistry 23 27624939
2006 Polymorphisms of the protein kinase C-beta gene (PRKCB1) accelerate kidney disease in type 2 diabetes without overt proteinuria. Diabetes care 23 16567829
2005 Central role of PKCbeta in neointimal expansion triggered by acute arterial injury. Circulation research 23 15662033
2005 Co-expression/co-location of S100 proteins (S100B, S100A1 and S100A2) and protein kinase C (PKC-beta, -eta and -zeta) in a rat model of cerebral basilar artery vasospasm. Neuropathology and applied neurobiology 23 16281914
2024 Schisandrin A alleviates renal fibrosis by inhibiting PKCβ and oxidative stress. Phytomedicine : international journal of phytotherapy and phytopharmacology 22 38382281
2021 Promoter Methylation of PRKCB, ADAMTS12, and NAALAD2 Is Specific to Prostate Cancer and Predicts Biochemical Disease Recurrence. International journal of molecular sciences 22 34198725
2018 Single Quantum Dot Imaging Reveals PKCβ-Dependent Alterations in Membrane Diffusion and Clustering of an Attention-Deficit Hyperactivity Disorder/Autism/Bipolar Disorder-Associated Dopamine Transporter Variant. ACS chemical neuroscience 22 30153408
2015 Homocysteine facilitates LOX-1 activation and endothelial death through the PKCβ and SIRT1/HSF1 mechanism: relevance to human hyperhomocysteinaemia. Clinical science (London, England : 1979) 22 25982096
2014 PKCβ positively regulates RANKL-induced osteoclastogenesis by inactivating GSK-3β. Molecules and cells 22 25256217
2021 P2X7 Receptor Deficiency Ameliorates STZ-induced Cardiac Damage and Remodeling Through PKCβ and ERK. Frontiers in cell and developmental biology 21 34395424
2017 LY333531, a PKCβ inhibitor, attenuates glomerular endothelial cell apoptosis in the early stage of mouse diabetic nephropathy via down-regulating swiprosin-1. Acta pharmacologica Sinica 21 28414198
2013 IL-33 attenuates anoxia/reoxygenation-induced cardiomyocyte apoptosis by inhibition of PKCβ/JNK pathway. PloS one 21 23457506
2011 Role for PKCβ in enhanced endothelin-1-induced pulmonary vasoconstrictor reactivity following intermittent hypoxia. American journal of physiology. Lung cellular and molecular physiology 21 21803871
2007 Retrospective analysis of protein kinase C-beta (PKC-beta) expression in lymphoid malignancies and its association with survival in diffuse large B-cell lymphomas. Biology direct 20 17313671
2000 Murine colonic mucosa hyperproliferation. II. PKC-beta activation and cPKC-mediated cellular CFTR overexpression. American journal of physiology. Gastrointestinal and liver physiology 20 10801269
2011 PKCβ-dependent phosphorylation of the glycine transporter 1. Neurochemistry international 19 21864610
2009 Molecular targeting of the PKC-beta inhibitor enzastaurin (LY317615) in multiple myeloma involves a coordinated downregulation of MYC and IRF4 expression. Hematological oncology 19 18759374
2004 Protein kinase C (PKC) beta modulates serine phosphorylation of insulin receptor substrate-1 (IRS-1)--effect of overexpression of PKCbeta on insulin signal transduction. Endocrine research 19 15473137
2001 Negative regulation of ligand-initiated Ca(2+) uptake by PKC-beta II in differentiated HL60 cells. American journal of physiology. Cell physiology 19 11443050
2019 Hyper-methylation of AVPR1A and PKCΒ gene associated with insensitivity to arginine vasopressin in human pre-eclamptic placental vasculature. EBioMedicine 18 31175056
2018 The PKCβ-p66shc-NADPH oxidase pathway plays a crucial role in diabetic nephropathy. The Journal of pharmacy and pharmacology 18 30417389
2016 SLA-PGN-primed dendritic cell-based vaccination induces Th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of PKCβ. Pathogens and disease 18 27150838
2006 Selective role of PKCbeta enzymatic function in regulating cell survival mediated by B cell antigen receptor cross-linking. Immunology letters 18 16564096
2006 RBCK1, a protein kinase CbetaI (PKCbetaI)-interacting protein, regulates PKCbeta-dependent function. The Journal of biological chemistry 18 17121852
2002 Lack of protein kinase C (PKC)-beta and low PKC-alpha, -delta, -epsilon, and -zeta isozyme levels in proliferating human melanoma cells. International journal of oncology 18 11894137
2020 Chronic morphine regulates TRPM8 channels via MOR-PKCβ signaling. Molecular brain 17 32290846
2015 Bone marrow stroma-induced resistance of chronic lymphocytic leukemia cells to arsenic trioxide involves Mcl-1 upregulation and is overcome by inhibiting the PI3Kδ or PKCβ signaling pathways. Oncotarget 17 26540567
2008 Activation of PKCbeta(II) and PKCtheta is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation. Biochemical and biophysical research communications 17 18211822
2008 Surface plasmon resonance biosensor detects the downstream events of active PKCbeta in antigen-stimulated mast cells. Biosensors & bioelectronics 17 18339533
2004 Effect of PKCbeta on retinal oxygenation response in experimental diabetes. Investigative ophthalmology & visual science 17 14985314
2020 PKCβ/NF-κB pathway in diabetic atrial remodeling. Journal of physiology and biochemistry 16 33085045

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