Affinage

PRKD1

Serine/threonine-protein kinase D1 · UniProt Q15139

Length
912 aa
Mass
101.7 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 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

PRKD1 (PKD/PKCμ) is a diacylglycerol- and phorbol ester-activated serine/threonine kinase that couples lipid second-messenger signaling to membrane trafficking, cytoskeletal dynamics, and cell-fate decisions (PMID:7836415, PMID:11729268). It is activated in cells through a PKC-dependent relay in which novel PKC isoforms (PKCε/η) transphosphorylate the PKD activation loop (Ser738/742), a step distinct from and downstream of its DAG-driven membrane recruitment (PMID:8947045, PMID:10471840, PMID:11741879); activation can also proceed through Gq-family and Gβγ-coupled GPCR inputs (PMID:15824133, PMID:22227248). At the trans-Golgi network, DAG binding recruits PKD where a Gβγ→PLCβ3→PKCη→PKD cascade activates it to drive fission of basolateral transport carriers, acting through PI4KIIIβ activation and CERT/OSBP phosphorylation and through direct phosphorylation of PARP12 that licenses Golgin-97 ADP-ribosylation for E-cadherin transport (PMID:15824133, PMID:17492941, PMID:18086912, PMID:21421913, PMID:34969853). PKD additionally governs Golgi integrity during the cell cycle via a Raf–MEK1 axis and drives mitotic mitochondrial fission by phosphorylating MFF, a step required for faithful chromosome segregation (PMID:23242995, PMID:34010649). In the cytoplasm PKD relays GPCR and antigen-receptor signals and phosphorylates a diverse substrate set—EGFR T654/T669 to suppress JNK signaling, Rabaptin-5 Ser407 to direct αvβ3 integrin recycling and invasion, cortactin and SSH2 to control actin-based migration and chemotaxis, and Vps34 to promote autophagy under oxidative stress (PMID:10523301, PMID:17707375, PMID:16563698, PMID:22095288, PMID:22975325, PMID:25568344). PRKD1 is epigenetically silenced by promoter methylation in invasive breast cancer where it maintains the epithelial phenotype and suppresses metastasis, yet as a direct Twist1 transcriptional target it can also drive epithelial dissemination through β-catenin and Tau phosphorylation; a recurrent activating E710D mutation marks polymorphous low-grade adenocarcinoma of the salivary gland (PMID:23971832, PMID:25240283, PMID:31676574).

Mechanistic history

Synthesis pass · year-by-year structured walk · 34 steps
  1. 1995 High

    Established PRKD1 as a distinct DAG/phorbol ester-responsive serine/threonine kinase rather than a conventional PKC, defining its founding biochemical identity.

    Evidence In vitro kinase assays with syntide-2, phorbol ester binding by bacterially expressed N-terminal domain, COS cell autophosphorylation

    PMID:7836415

    Open questions at the time
    • Physiological substrates not yet identified
    • Cellular activation pathway not yet defined
  2. 1996 High

    Showed PKD activation in cells is PKC-dependent, placing it downstream of novel PKC isoforms and resolving how DAG signals reach the kinase.

    Evidence Pharmacological PKC inhibition, constitutively active PKCε/η co-transfection, cell-free reversal in COS-7 cells

    PMID:8947045

    Open questions at the time
    • Direct phosphorylation site on PKD not yet mapped
    • Identity of the upstream kinase at endogenous sites unconfirmed in 1996
  3. 1996 High

    Linked PKD to antigen receptor signaling by showing it associates with and modulates the BCR/Syk/PLCγ module, extending its role into immune-receptor relays.

    Evidence Co-IP from B cells, in vitro kinase assays on Syk/PLCγ1, DT40 genetic epistasis

    PMID:8885868

    Open questions at the time
    • In vivo relevance of Syk/PLCγ1 phosphorylation not established
    • Whether feedback role is physiologically dominant unknown
  4. 1999 High

    Identified EGFR T654/T669 as direct PKD substrates whose phosphorylation suppresses JNK signaling, giving PKD a defined receptor-modulatory output.

    Evidence EGFR site mutagenesis, PKD overexpression, JNK activity assays in Rat-1 and glioblastoma cells

    PMID:10523301

    Open questions at the time
    • Endogenous stoichiometry of EGFR phosphorylation unknown
    • Direct in vitro demonstration limited
  5. 1999 High

    Dissected PKD membrane translocation from kinase activation, establishing the CRD as the targeting module independent of catalytic activity.

    Evidence Real-time GFP-PKD imaging, P287G CRD mutant, kinase assays

    PMID:10471840

    Open questions at the time
    • Lipid ligand specificity of each C1 subdomain not resolved here
    • Subcellular target of translocation beyond plasma membrane not addressed
  6. 2000 High

    Demonstrated transient receptor-triggered membrane targeting followed by sustained cytosolic activity, defining how PKD spatiotemporally disseminates antigen-receptor signals.

    Evidence Subcellular fractionation, domain deletion mutants, kinase assays in B cells and mast cells

    PMID:10856238

    Open questions at the time
    • Cytosolic substrates of recycled active PKD not identified
    • Mechanism sustaining cytosolic activity unclear
  7. 2001 High

    Defined PKD as a regulator of TGN-to-surface trafficking, recruited by DAG and required for fission of transport carriers.

    Evidence DAG manipulation, TGN localization, protein transport assays

    PMID:11729268

    Open questions at the time
    • Direct fission substrates not yet identified
    • Carrier cargo selectivity not addressed
  8. 2001 High

    Mapped PKCη as the direct activation-loop kinase (Ser738/742) for PKD, completing the upstream PKC→PKD writer relationship and linking it to ERK/SRE signaling.

    Evidence In vitro phosphorylation, confocal colocalization, constitutively active PKCη, reporter assays

    PMID:11741879

    Open questions at the time
    • Whether PKCη is the sole physiological activation-loop kinase unknown
    • Context-specificity versus PKCε not resolved
  9. 2001 High

    Resolved the Golgi recruitment logic—dual N-terminal hydrophobic plus CRD requirement, constitutive and activation-independent—and ordered recruitment before activation-loop phosphorylation.

    Evidence GFP-fusion deletion mutants, FRAP, fractionation, phospho-specific blots in HeLa

    PMID:11777941

    Open questions at the time
    • Identity of the trans-acting Golgi activation-loop kinase not established here
    • Lipid versus protein contributions to Golgi anchoring unresolved
  10. 2001 Medium

    Extended PKD activation to GPCR/Gi-coupled inputs (LPA, angiotensin II) in epithelial cells and identified Ser916 autophosphorylation as an activity marker.

    Evidence Intact-cell kinase assays, pertussis toxin, Ser916 autophosphorylation detection in IEC cells

    PMID:11245610

    Open questions at the time
    • Single lab
    • Downstream effectors of LPA/AngII-induced PKD not identified
  11. 2002 Medium

    Showed PKD is activated downstream of PKC in platelets by GPCR and tyrosine kinase agonists, broadening its receptor-relay role to hemostatic cells.

    Evidence Platelet agonist activation assays, PKC inhibition, kinase activity measurement

    PMID:12393506

    Open questions at the time
    • Functional platelet substrates of PKD not identified
    • Single lab
  12. 2005 High

    Established the Gβγ→PKCη→PKD axis at the TGN with epistatic ordering, defining the heterotrimeric G-protein input to Golgi carrier formation.

    Evidence Dominant-negative/constitutively active constructs, Golgi fragmentation and transport assays, kinase-dead PKD epistasis

    PMID:15824133

    Open questions at the time
    • Source of Gβγ at the Golgi not defined
    • Link to PLC isoform not yet identified at this step
  13. 2007 High

    Identified PLCβ3 as the specific DAG-generating PLC upstream of PKCη/PKD at the TGN, completing the lipid-signaling input to carrier fission.

    Evidence Isoform-selective siRNA, PI-PLC inhibitor/activator, activation-loop phospho-blot, transport assays

    PMID:17492941

    Open questions at the time
    • How PLCβ3 is recruited/activated at the Golgi unclear
    • Spatial coupling to Gβγ not directly imaged
  14. 2007 High

    Defined PKD's mechanistic role as a dimeric membrane-fission machine controlling carrier size and preventing uncontrolled TGN vesiculation.

    Evidence siRNA depletion, constitutively active PKD, EM and fluorescence Golgi morphology, transport assays

    PMID:18086912

    Open questions at the time
    • Direct fission-effector substrates not identified in this study
    • Structural basis of dimeric fission unknown
  15. 2007 High

    Established PKD as a negative regulator of cell migration acting through cortactin phosphorylation at the leading edge.

    Evidence Confocal colocalization, F-actin pulldown, in vitro cortactin kinase assay, dominant-negative/siRNA migration assays

    PMID:17707375

    Open questions at the time
    • Cortactin phospho-site functional consequence on actin not fully mapped
    • Reconciliation with pro-invasive roles unclear
  16. 2008 High

    Identified type IIα PIP kinase T376 as an inhibitory PKD substrate, linking PKD to phosphoinositide pool regulation.

    Evidence In vitro kinase assay, phospho-specific antibody, T376 mutagenesis, pharmacological PKD inhibition

    PMID:16563698

    Open questions at the time
    • Physiological context of PIP kinase inhibition not defined
    • Downstream lipid consequences not measured
  17. 2008 Medium

    Showed PKD/PKD2 mediate neurotensin-induced Hsp27 Ser-82 phosphorylation in parallel to p38, extending PKD substrate scope in cancer cells.

    Evidence siRNA of PKD/PKD2, phospho-Hsp27 blots, PKC/p38 inhibition, overexpression in PANC-1

    PMID:17570131

    Open questions at the time
    • Direct phosphorylation versus indirect not distinguished
    • Single lab
  18. 2009 Medium

    Linked PKD activity to microtubule-dependent Golgi integrity using a Golgi-targeted activity reporter.

    Evidence Genetically encoded TGN-targeted PKD reporter, dominant-negative/siRNA, nocodazole

    PMID:19416469

    Open questions at the time
    • Mechanistic substrate linking PKD to microtubule-driven dispersal unknown
    • Single lab
  19. 2009 High

    Established an inhibitory p38δ→PKD1 axis controlling insulin secretion and β-cell survival in vivo, integrating PKD into endocrine physiology.

    Evidence p38δ knockout mice, PKD1 inhibition in islets, glucose tolerance and insulin secretion assays

    PMID:19135240

    Open questions at the time
    • Direct p38δ phosphorylation site on PKD1 not mapped here
    • PKD1 secretory substrates in β cells not identified
  20. 2011 High

    Identified Vps34 as a PKD substrate activating PI(3)P production and autophagosome formation under oxidative stress, downstream of DAPk.

    Evidence PKD-Vps34 co-IP, PI(3)P measurement, LC3 puncta assay, DAPk epistasis, autophagosome localization

    PMID:22095288

    Open questions at the time
    • Vps34 phospho-site not mapped
    • Specificity of stress conditions not fully defined
  21. 2011 Medium

    Showed PKD1 promotes NF-κB and suppresses p38 in oxidative-stress survival of intestinal epithelium, defining a cytoprotective signaling output.

    Evidence siRNA, wild-type/kinase-dead overexpression, phospho-blots, NF-κB translocation

    PMID:19059215

    Open questions at the time
    • Direct PKD1 substrate in NF-κB/p38 pathways unknown
    • Single lab
  22. 2011 High

    Defined PKD-Rabaptin-5 Ser407 phosphorylation as the switch directing αvβ3 integrin recycling and invasive motility, giving PKD a pro-invasive trafficking role.

    Evidence In vitro kinase assay, phospho-antibody, Rab4/Rab5 co-IP, Ser407 mutagenesis, integrin recycling and 3D invasion assays

    PMID:22975325

    Open questions at the time
    • How this reconciles with PKD anti-migratory roles unclear
    • Upstream PKD activation in this context not fully mapped
  23. 2011 Medium

    Synthesized the lipid-remodeling arm of PKD trafficking—PI4KIIIβ activation, CERT/OSBP phosphorylation, and DAG→PA→LPA conversion for fission.

    Evidence Review synthesizing biochemical evidence on PI4KIIIβ and CERT/OSBP

    PMID:21421913

    Open questions at the time
    • Review format aggregating prior data
    • Quantitative lipid flux at fission sites not directly resolved
  24. 2012 High

    Placed PKD upstream of a mitotic Raf–MEK1 axis controlling Golgi fragmentation and G2/M progression.

    Evidence siRNA of PKD1/2, cell cycle analysis, Raf/MEK blots, constitutively active MEK1 rescue, Golgi FRAP

    PMID:23242995

    Open questions at the time
    • Direct PKD substrate connecting to Raf-1 activation unknown
    • Mechanism of mitotic PKD activation not defined
  25. 2013 High

    Established PRKD1 as an epigenetically silenced metastasis suppressor in breast cancer whose re-expression maintains the epithelial phenotype.

    Evidence Methylation-specific PCR, bisulfite sequencing, decitabine xenograft rescue, invasion and metastasis imaging

    PMID:23971832

    Open questions at the time
    • Mechanism of EMT suppression at substrate level not defined here
    • Reconciliation with pro-invasive substrate phosphorylation unaddressed
  26. 2013 Medium

    Implicated a purinergic→PKC→PKD cascade in Schwann cell GDNF upregulation after nerve injury, extending PKD into neural injury responses.

    Evidence Pharmacological PKC/PKD inhibition, siRNA, GDNF expression assays

    PMID:23553603

    Open questions at the time
    • Direct transcriptional mechanism unknown
    • Limited mechanistic detail
  27. 2014 Medium

    Identified the recurrent activating E710D mutation as a likely driver of polymorphous low-grade adenocarcinoma, establishing PRKD1 as a cancer oncogenic alteration.

    Evidence Tumor sequencing, functional kinase activity assay of E710D versus wild-type

    PMID:25240283

    Open questions at the time
    • Structural basis of constitutive activation not resolved
    • Downstream oncogenic substrates in PLGA unknown
  28. 2015 High

    Showed PKD family kinases mediate GPCR-driven YAP inactivation via Lats2, connecting PKD to Hippo-pathway control of growth genes.

    Evidence PKD inhibitors, PKD1/2/3 triple siRNA, phospho-YAP blots, fractionation, target gene qRT-PCR

    PMID:27369082

    Open questions at the time
    • Direct PKD substrate in the Lats2/YAP module not identified
    • Isoform-specific contributions not separated
  29. 2015 High

    Defined the GPCR→PLCγ2→PKCβ→PKD1→SSH2 axis driving neutrophil chemotaxis via cofilin/actin control.

    Evidence siRNA epistasis, PKCβ-PKD1 co-IP, in vitro SSH2 kinase assay, cofilin blots, chemotaxis assays

    PMID:25568344

    Open questions at the time
    • SSH2 phospho-site not mapped here
    • Reconciliation with other PKD migratory roles unclear
  30. 2015 High

    Identified PRKD1 as a direct Twist1 transcriptional target required for epithelial dissemination via β-catenin and Tau phosphorylation, revealing a context-dependent pro-metastatic role.

    Evidence 3D mammary organoids, Twist1 overexpression, ChIP-PCR, Prkd1 inhibition/shRNA, phosphoproteomics, in vivo tumor model

    PMID:31676574

    Open questions at the time
    • Direct versus indirect β-catenin/Tau phosphorylation not fully resolved
    • Reconciliation with PKD1 metastasis-suppressor role context-dependent
  31. 2016 Medium

    Linked PKD-1 to nuclear FoxO1-HDAC7 complex formation repressing endothelial CD36 and driving proangiogenic reprogramming.

    Evidence DNA-binding assay, ChIP, FoxO1-HDAC7 co-IP, PLA, angiogenesis assays

    PMID:27013613

    Open questions at the time
    • Direct PKD substrate in this complex unknown
    • Single lab
  32. 2018 Medium

    Defined a Rho network (GEF-H1/DLC3/PLCε) regulating PKD activation at the TGN for focal-adhesion-directed exocytosis.

    Evidence Genetically encoded PKD activity reporter, siRNA of Rho components, Rab6 carrier imaging

    PMID:30028295

    Open questions at the time
    • How Rho input integrates with Gβγ/PLCβ3 axis unclear
    • Single lab
  33. 2021 High

    Identified MFF as a mitosis-specific PKD substrate driving mitochondrial fission required for chromosome segregation, extending PKD into mitotic organelle dynamics.

    Evidence In vitro kinase assay, phospho-antibody, phospho-mimetic/dead MFF mutants, chromosome segregation and checkpoint assays

    PMID:34010649

    Open questions at the time
    • Mechanism restricting MFF phosphorylation to mitosis unknown
    • Spatial control of mitotic PKD activation undefined
  34. 2022 High

    Established the PKD→PARP12→Golgin-97 ADP-ribosylation cascade as a selective mechanism for basolateral E-cadherin carrier fission at the TGN.

    Evidence In vitro kinase and ADP-ribosylation assays, mutagenesis of multiple sites, cargo transport and carrier fission imaging

    PMID:34969853

    Open questions at the time
    • PARP12 phospho-site and Golgin-97 acidic cluster generality across cargoes not fully defined
    • How this integrates with lipid-remodeling fission arm unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PKD1's opposing roles—epithelial-phenotype maintenance and metastasis suppression versus Twist1-driven pro-dissemination and pro-invasive integrin recycling—are reconciled within a single cell context remains unresolved.
  • No unified model reconciling anti- and pro-metastatic PKD1 outputs
  • Determinants of substrate selection across contexts unknown
  • Spatial control of distinct PKD1 activity pools not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016740 transferase activity 5 GO:0008289 lipid binding 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005794 Golgi apparatus 7 GO:0005829 cytosol 3 GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 1
Partners
MFFPARP12PLCB3PRKCEPRKCHRABEP5SSH2VPS34

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 PKD (PRKD1) is a novel phorbol ester and diacylglycerol-stimulated serine/threonine protein kinase. A bacterially expressed NH2-terminal domain exhibited high affinity phorbol ester binding (Kd = 35 nM). The catalytic domain phosphorylates the peptide substrate syntide-2 on serine. Phorbol esters and diacylglycerol in the presence of phospholipids stimulate syntide-2 kinase activity and autophosphorylation in COS cells. Substrate specificity differs from PKC family members. In vitro kinase assay with synthetic peptide substrates, phorbol ester binding assay with bacterially expressed domain, COS-7 cell transfection and immunoprecipitation kinase assay The Journal of biological chemistry High 7836415
1996 PKD is activated in living cells through a PKC-dependent signal transduction pathway. Phorbol esters, membrane-permeant DAG, and serum growth factors rapidly induced PKD activation. PKC inhibitors (GF I and Ro 31-8220) completely abrogated cellular PKD activation but did not inhibit PKD activity when added directly in vitro. Co-transfection with constitutively active PKCε and PKCη (but not PKCζ) strongly induced PKD activation in COS-7 cells via phosphorylation. Intact cell activation assays, immunopurified kinase activity, co-transfection with constitutively active PKC mutants, alkaline phosphatase reversal of activation, pharmacological PKC inhibition The EMBO journal High 8947045
1996 PKCμ (PRKD1) associates with the B cell antigen receptor (BCR) complex, co-precipitating with Syk and PLCγ1/2. BCR cross-linking activates PKCμ in a Syk-dependent and partially Btk-dependent manner. In vitro phosphorylation showed Syk and PLCγ1 are potential PKCμ substrates. PKCμ can down-regulate Syk-mediated phosphorylation of PLCγ1 in vitro, suggesting a negative feedback role. Co-immunoprecipitation from B cells, in vitro kinase assay with fusion protein substrates, DT40 B cell mutant analysis (genetic epistasis) Immunity High 8885868
1999 PKD directly phosphorylates threonines T654 and T669 of the EGF receptor. PDGF (but not EGF) activates PKD in Rat-1 cells. PKD-mediated dual phosphorylation of EGFR T654/T669 suppresses EGF-induced JNK activation. An EGFR mutant (T654/669E) mimicking phosphorylation was incapable of activating JNK. Overexpression of PKD in glioblastoma cells blocked EGF- and PDGF-induced JNK activation. Site-directed mutagenesis of EGFR phosphorylation sites, overexpression of PKD, JNK activity assays, cell-type specific PKD activation assays The EMBO journal High 10523301
1999 PKD/PKCμ translocates from cytosol to plasma membrane upon phorbol ester treatment in a cysteine-rich domain (CRD)-dependent manner, as visualized by GFP-PKD fusion protein in real time. A single amino acid substitution (P287G) in the second cysteine-rich motif prevented PDB-induced membrane translocation without affecting PKD kinase activation, demonstrating that PKD translocation and activation are dissociable processes. Real-time live cell imaging of GFP-PKD fusion protein, site-directed mutagenesis of CRD domain, kinase activity assay FEBS letters High 10471840
2000 PKD is present in the cytosol of quiescent B cells and mast cells and rapidly translocates to the plasma membrane upon antigen receptor triggering. Membrane redistribution requires the DAG-binding domain but is independent of catalytic activity and PH domain integrity. Membrane targeting is transient (returns to cytosol within 10 min), yet the membrane-recycled PKD remains active in the cytosol for several hours, establishing spatiotemporal dissemination of antigen receptor signals. Subcellular fractionation, kinase activity assays, domain deletion mutants, antigen receptor triggering in B cells and mast cells The EMBO journal High 10856238
2001 PKD binds diacylglycerol (DAG) and this binding is necessary for its recruitment to the trans-Golgi network (TGN). Reducing cellular DAG levels inhibited PKD recruitment and blocked protein transport from the TGN to the cell surface. PKD regulates the fission of transport carriers destined to the cell surface from the TGN. DAG manipulation (pharmacological and genetic reduction), PKD localization assay at TGN, protein transport assays to cell surface Science High 11729268
2001 PKCη directly phosphorylates PKD (PKCμ) activation loop serines (Ser738/742) in vitro, leading to PKD activation. PKD colocalizes with PKCη in a PH domain-dependent manner. PKCη-mediated PKD activation stimulates p42 MAPK/ERK cascade and reporter gene transcription via SRE, while simultaneously reducing PKCη-mediated JNK activation. In vitro phosphorylation assay showing PKCη phosphorylates PKD activation loop, confocal colocalization, co-expression of constitutively active PKCη, kinase substrate phosphorylation assay, reporter gene assay The Journal of biological chemistry High 11741879
2001 PKD is rapidly activated in intestinal epithelial cells (IEC-6, IEC-18) by phorbol esters, lysophosphatidic acid (LPA), and angiotensin II through a PKC-dependent pathway. LPA-induced PKD activation is prevented by pertussis toxin, indicating Gi coupling. PKD activation is tightly associated with autophosphorylation at serine 916. PKD does not undergo downregulation after prolonged phorbol ester treatment, unlike conventional/novel PKCs. Intact cell kinase assays, PKC inhibitor treatment, pertussis toxin treatment, autophosphorylation detection at Ser916 American journal of physiology. Cell physiology Medium 11245610
2002 Golgi localization of PKCμ (PRKD1) requires both the NH2-terminal hydrophobic region and the cysteine-rich region; deletion of either completely abrogates Golgi localization. The NH2-terminal PKCμ fragment is sufficient for Golgi membrane association. Golgi recruitment is constitutive, rapid, and independent of activation loop phosphorylation or kinase activity. A sequential activation process occurs: Golgi recruitment precedes and is required for activation loop phosphorylation (Ser738/742) by a trans-acting kinase, followed by auto- and transphosphorylation of NH2-terminal serines. Confocal microscopy of GFP-fusion deletion mutants in HeLa cells, FRAP analysis, cell fractionation, phospho-specific western blot The Journal of cell biology High 11777941
2002 PKD (PKCμ) is expressed in human platelets and rapidly activated by receptors coupled to heterotrimeric G-proteins or tyrosine kinases. PKD activation in platelets is mediated downstream of PKC. Strong agonists (convulxin via GPVI, thrombin) cause sustained PKD activation; thromboxane mimetic U46619 causes transient activation. Gi-coupled receptor agonists potentiate PKD activation by submaximal PLC-coupled agonist concentrations. Platelet activation assays with multiple agonists, PKC inhibitor treatment, kinase activity measurement Blood Medium 12393506
2005 PKD is activated specifically by G protein subunits β1γ2 and β3γ2 via the Golgi apparatus-associated PKCη. PKD is activated at the TGN through a Gβγ→PKCη→PKD axis. Compromising PKCη kinase activity inhibits protein transport from TGN to cell surface. Constitutively active PKCη caused Golgi fragmentation that was inhibited by kinase-inactive PKD, placing PKD downstream of PKCη in the vesicle-generating pathway. Dominant-negative and constitutively active kinase constructs, Golgi fragmentation assay, protein transport assay, epistasis by kinase-dead PKD The Journal of cell biology High 15824133
2006 The C1b domain of PKD isoforms binds phorbol esters with high affinity, while the C1a domain has non-consensus residues that mainly contribute to structural fold rather than ligand binding. C1a and C1b in intact C1a-C1b of PKD1 show opposite selectivity for phorbol esters (PDBu) and DAG (DOG). A conserved lysine at position 22 in C1b accounts for weaker DAG affinity. Mutation of C1a in full-length PKD3-GFP reduces DOG-induced plasma membrane translocation but not PMA-induced translocation. Radioligand binding assay with [3H]PDBu, site-directed mutagenesis of C1 domain residues, GFP-PKD translocation assay in living cells The Biochemical journal High 18076381
2007 PLCβ3 is the specific phospholipase C isoform required for PKD1 activation at the TGN. Gβγ-dependent Golgi fragmentation, PKD1 activation loop phosphorylation, and TGN-to-plasma membrane transport were inhibited by a PI-PLC inhibitor (U73122) and by siRNA knockdown of PLCβ3 (but not other PI-PLC isoforms). A PI-PLC activator (m-3M3FBS) induced Golgi vesiculation and PKD1 activation loop phosphorylation. PLCβ3 acts upstream of PKCη and PKD in the vesicle-generating pathway by producing DAG. siRNA knockdown of individual PLCβ isoforms, pharmacological PI-PLC inhibition and activation, PKD1 activation loop phosphorylation western blot, TGN-to-plasma membrane transport assay The Biochemical journal High 17492941
2007 PKD depletion by siRNA inhibits TGN-to-cell surface trafficking, while expression of constitutively active PKD converts TGN into small vesicles. PKD is required for membrane fission to generate transport carriers, and this activity controls the size of transport carriers and prevents uncontrolled vesiculation of TGN. PKD functions as a dimer at the TGN for membrane fission. siRNA depletion of PKD, constitutively active PKD expression, electron microscopy and fluorescence microscopy of Golgi morphology, protein transport assays The Journal of cell biology High 18086912
2007 PKD is recruited to the leading edge of migrating cells where it co-localizes with F-actin, Arp3, and cortactin. PDGF activates PKD and recruits it to the leading edge. PKD directly interacts with F-actin and phosphorylates cortactin in vitro. Dominant-negative PKD or PKD siRNA enhanced cell migration, while wild-type PKD overexpression reduced migration, establishing a negative regulatory function of PKD in cell migration. Confocal co-localization, in vitro pulldown with F-actin, in vitro kinase assay for cortactin phosphorylation, dominant-negative overexpression, siRNA knockdown, migration assay FEBS letters High 17707375
2008 PKD phosphorylates type IIα PIP kinase on activation loop threonine T376, inhibiting enzyme activity. A phospho-specific antibody confirmed T376 phosphorylation in living cells, enhanced when PKD was activated. Mutation of T376 to aspartate (phosphomimetic) significantly inhibited PIP kinase activity. PKD was identified as the responsible kinase by pharmacological studies and in vitro confirmation. In vitro phosphorylation assay, phospho-specific antibody, site-directed mutagenesis of T376, pharmacological PKD inhibition in cells Cellular signalling High 16563698
2008 PKD and PKD2 mediate neurotensin-induced phosphorylation of Hsp27 at Ser-82 in PANC-1 pancreatic cancer cells through a PKC-dependent pathway. siRNA knockdown of PKD or PKD2 individually reduced Hsp27 Ser-82 phosphorylation; combined knockdown of both virtually abolished it. This pathway operates in parallel to p38 MAPK-mediated Hsp27 phosphorylation. siRNA knockdown of PKD and PKD2, phospho-specific western blot for Hsp27 Ser-82, pharmacological inhibition of PKC and p38 MAPK, PKD overexpression in stably transfected cells Journal of cellular biochemistry Medium 17570131
2009 A Golgi-targeted PKD activity reporter (PKD-specific substrate fused to EGFP targeted to TGN via p230 GRIP domain) revealed that nocodazole-induced Golgi dispersal is associated with local PKD activation. Dominant-negative PKD or PKD siRNA depletion blocked nocodazole-induced Golgi break-up, identifying a link between PKD activity and microtubule cytoskeleton in regulating Golgi complex integrity. Genetically encoded Golgi-targeted PKD activity reporter, phospho-specific antibody validation, ratiometric fluorescence imaging, dominant-negative PKD expression, siRNA knockdown, nocodazole treatment Traffic Medium 19416469
2009 p38δ MAPK catalyzes an inhibitory phosphorylation of PKD1, thereby attenuating stimulated insulin secretion from pancreatic β cells. Deletion of p38δ results in pronounced PKD activation and enhanced insulin exocytosis. Inhibition of PKD1 reverses enhanced insulin secretion in p38δ-deficient islets. The p38δ-PKD1 pathway integrates regulation of insulin secretory capacity and β cell survival. p38δ knockout mice, PKD1 inhibition in isolated islets, glucose tolerance tests, in vivo and ex vivo insulin secretion measurements, genetic epistasis (p38δ KO + PKD1 inhibition) Cell High 19135240
2011 PKD phosphorylates Vps34 (a lipid kinase), leading to Vps34 activation, PI(3)P formation, and autophagosome formation in response to oxidative stress. PKD is found in the same molecular complex with Vps34 by co-immunoprecipitation. PKD is activated by DAPk (death-associated protein kinase) upstream in this cascade. PKD is recruited to LC3-positive autophagosomal membranes. Co-immunoprecipitation of PKD-Vps34 complex, PI(3)P measurement, autophagosome formation assay (LC3 puncta), epistasis with DAPk, PKD localization to autophagosomes Cell death and differentiation High 22095288
2011 PKD1 promotes NF-κB activation and suppresses p38 MAPK in response to H2O2 in intestinal epithelial cells, thereby protecting against apoptosis. PKD1 siRNA inhibited H2O2-induced NF-κB activation, p65 translocation, and IκBα phosphorylation. Wild-type PKD1 overexpression reduced p38 MAPK and MKK3/6 phosphorylation, while kinase-dead PKD1 increased it. PKD1 does not affect ERK1/2 or JNK phosphorylation. siRNA knockdown, overexpression of wild-type and kinase-dead PKD1, phospho-specific western blots for NF-κB pathway components and MAPKs, NF-κB translocation assay Biochemical and biophysical research communications Medium 19059215
2011 PKD mediates PDGF-dependent αvβ3 integrin recycling through phosphorylation of Rabaptin-5 at Ser407. PKD phosphorylation of Rabaptin-5 Ser407 is necessary and sufficient for PDGF-dependent short-loop αvβ3 recycling and inhibition of α5β1 recycling. Rab4 (not Rab5) interacts with phosphorylated Rabaptin-5 at the leading edge to promote αvβ3 delivery, driving persistent cell motility and invasion. In vitro kinase assay identifying Rabaptin-5 Ser407 as PKD substrate, phospho-specific antibody, Rab4/Rab5 co-immunoprecipitation with phospho-Rabaptin-5, mutagenesis of Ser407, integrin recycling assay, 2D migration and 3D invasion assay Developmental cell High 22975325
2011 PKD activates PI4KIIIβ (phosphatidylinositol 4-kinase IIIβ) at the TGN to promote PI4P production. PI4P then recruits OSBP and CERT which control sphingolipid and sterol levels. PKD subsequently phosphorylates OSBP and CERT to dissociate them from TGN. This drives sequential DAG→PA→LPA lipid conversion necessary for membrane fission to generate cell surface transport carriers. Review synthesizing biochemical evidence from preceding studies; includes lipid kinase activation and substrate phosphorylation evidence Cold Spring Harbor perspectives in biology Medium 21421913
2012 PKD controls mitotic Golgi fragmentation via a Raf-MEK1 pathway. siRNA depletion of PKD1 and PKD2 causes G2 cell cycle arrest and prevents mitosis entry. PKD inhibition blocks mitotic Raf-1 and MEK activation, and consequently mitotic Golgi fragmentation; expression of active MEK1 rescues the PKD-depleted phenotype. FRAP analysis showed PKD is crucial for cleavage of non-compact Golgi membrane zones in G2 phase. siRNA depletion of PKD1/PKD2, cell cycle analysis, Raf/MEK activation western blot, constitutively active MEK1 rescue, Golgi FRAP analysis Molecular biology of the cell High 23242995
2013 PRKD1 promoter is aberrantly methylated and silenced in invasive breast cancer cells. Re-expression of PKD1 via decitabine (DNA methyltransferase inhibitor) restores PKD1 expression and blocks tumor metastasis to the lung in a xenograft model in a PKD1-dependent manner. PKD1 expression maintains the epithelial phenotype by preventing EMT in normal mammary gland cells. Methylation-specific PCR, bisulfite deep sequencing, decitabine treatment in vitro and in vivo xenograft model, transwell invasion assay, in vivo bioluminescence imaging of metastasis Breast cancer research High 23971832
2013 Nerve injury-induced GDNF upregulation in Schwann cells is mediated by a purinergic receptor→PKC→PKD signaling cascade. Activation of Schwann cell purinergic receptors leads to PKC activation, which activates PKD, which drives increased GDNF transcription. Pharmacological inhibition of PKC and PKD, siRNA knockdown, GDNF expression assays in Schwann cells following nerve injury model Glia Medium 23553603
2014 PRKD1 hotspot somatic mutation E710D (p.Glu710Asp) is a kinase-activating alteration found in 72.9% of polymorphous low-grade adenocarcinomas (PLGAs) of salivary glands but not in other salivary gland tumors. Functional studies demonstrated this mutation constitutively activates PRKD1 kinase activity, likely acting as a driver of PLGA. Tumor sequencing, functional characterization of kinase activity of E710D mutant vs wild-type Nature genetics Medium 25240283
2015 PRKD1 is a direct transcriptional target of Twist1 and is not expressed in normal mammary epithelium. Prkd1 is required for Twist1-induced epithelial dissemination: pharmacological and genetic Prkd1 inhibition blocks ECM-directed protrusions, epithelial release, and migration through ECM. Prkd1 induces phosphorylation of β-catenin (inactivating) and Tau (microtubule-depolymerizing) as part of its dissemination program. Prkd1 knockdown in vivo blocked primary tumor invasion and distant metastasis. 3D mammary organoid culture model, Twist1 overexpression, Prkd1 pharmacological inhibition and shRNA knockdown, ChIP-PCR confirming direct Twist1 binding to Prkd1 promoter, antibody-based phosphoproteomics, in vivo mouse tumor model Cancer research High 31676574
2015 GPCR activation induces biphasic YAP regulation in intestinal epithelial cells through PKD family kinases. PKD family inhibitors or siRNA-mediated knockdown of PKD1/PKD2/PKD3 prevented YAP phosphorylation at Ser127 and Ser397 via Lats2, cytoplasmic accumulation of YAP, and induction of YAP/TEAD-regulated genes (CTGF and Areg) in response to angiotensin II, vasopressin, or serum. PKD family inhibitors (CRT0066101, kb NB 142-70), siRNA knockdown of PKD1/2/3, phospho-specific western blot for YAP, nuclear-cytoplasmic fractionation, qRT-PCR of YAP target genes The Journal of biological chemistry High 27369082
2015 PKD1 promotes neutrophil chemotaxis through the GPCR→PLCγ2(PI3K-dependent)→PKCβ→PKD1→SSH2 signaling axis. PKCβ specifically interacts with PKD1 and is required for chemotaxis. PKD1 phosphorylates slingshot phosphatase 2 (SSH2), which regulates cofilin phosphorylation and actin cytoskeletal reorganization. siRNA knockdown of pathway components, co-immunoprecipitation of PKCβ-PKD1 interaction, in vitro kinase assay for SSH2 phosphorylation, cofilin phosphorylation western blot, chemotaxis assay Molecular biology of the cell High 25568344
2016 LPA-mediated CD36 transcriptional repression by PKD-1 involves PKD-1 signaling-mediated formation of a FoxO1-HDAC7 complex in the nucleus. PKD-1 promotes nuclear accumulation of HDAC7, where it interacts with FoxO1 to suppress endothelial CD36 transcription, leading to proangiogenic reprogramming including ephrin B2 expression. Avidin-biotin-conjugated DNA-binding assay, chromatin immunoprecipitation, co-immunoprecipitation of FoxO1-HDAC7 complex, proximal ligation assay, immunofluorescence, gene transfection, spheroid angiogenesis assay, in vivo Matrigel angiogenesis Arteriosclerosis, thrombosis, and vascular biology Medium 27013613
2018 A Rho signaling network comprising GEF-H1, the RhoGAP DLC3, and the Rho effector PLCε regulates PKD activation at trans-Golgi membranes. This molecular network coordinates formation of TGN-derived Rab6-positive transport carriers for localized exocytosis at focal adhesions. Genetically encoded PKD activity reporter (G-PKDrep), siRNA knockdown of Rho pathway components (GEF-H1, DLC3, PLCε), live cell imaging of Rab6 transport carriers, focal adhesion exocytosis assay eLife Medium 30028295
2021 PKD directly phosphorylates the mitochondrial fission factor MFF specifically during mitosis. PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic (but not interphase) cells. Phosphorylation of MFF by PKD is crucial for chromosome segregation and promotes cell survival by inhibiting adaptation of the mitotic checkpoint. In vitro kinase assay identifying MFF as PKD substrate during mitosis, phospho-specific antibody, expression of phospho-mimetic and phospho-dead MFF mutants, chromosome segregation assay, mitotic checkpoint analysis Cell reports High 34010649
2022 PKD directly phosphorylates PARP12 at the TGN, which is essential to stimulate PARP12 catalytic activity. Activated PARP12 then mono-ADP-ribosylates Golgin-97 at an acidic cluster in its coiled-coil domain, which is required for E-cadherin and VSVG carrier fission and transport from TGN to plasma membrane. PARP12/Golgin-97 ADP-ribosylation is selective for Golgin-97-dependent (not Golgin-245-dependent) basolateral cargo transport. In vitro kinase assay showing PKD phosphorylates PARP12, in vitro ADP-ribosylation assay of Golgin-97 by PARP12, mutagenesis of Golgin-97 acidic cluster and PARP12 phosphorylation site, cargo transport assay (E-cadherin, VSVG), live imaging of carrier fission Proceedings of the National Academy of Sciences High 34969853
2011 Gαq, but not the closely related Gα11, promotes PKD autophosphorylation at Ser748 (activation loop) in a PKC-independent manner. Gα11, Gα14, and Gα15 mediate PKD activation in a PKC-dependent manner. Gαq-specific PKC-independent PKD activation was also demonstrated using Pasteurella multocida toxin (selective Gαq activator) in Swiss 3T3 cells. COS-7 cell co-transfection with Gq-family Gα subunits, AlF4⁻ activation, PKC inhibitor (GF1) treatment, phospho-specific western blot for Ser744 (PKC transphosphorylation) and Ser748 (autophosphorylation), in vitro kinase assay Cellular signalling Medium 22227248

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Role of diacylglycerol in PKD recruitment to the TGN and protein transport to the plasma membrane. Science (New York, N.Y.) 350 11729268
2009 Characterization of PKD protein-positive exosome-like vesicles. Journal of the American Society of Nephrology : JASN 274 19158352
2006 PKD at the crossroads of DAG and PKC signaling. Trends in pharmacological sciences 274 16678913
2001 The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway. Current biology : CB 249 11553327
1996 Protein kinase D (PKD) activation in intact cells through a protein kinase C-dependent signal transduction pathway. The EMBO journal 223 8947045
2009 Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis. Cell 208 19135240
2010 Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1. Journal of the American Society of Nephrology : JASN 205 20075061
2011 Mutations in multiple PKD genes may explain early and severe polycystic kidney disease. Journal of the American Society of Nephrology : JASN 179 22034641
1999 The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease. The EMBO journal 174 9889186
2014 Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands. Nature genetics 169 25240283
2009 Chemical modifier screen identifies HDAC inhibitors as suppressors of PKD models. Proceedings of the National Academy of Sciences of the United States of America 168 19966229
1995 Expression and characterization of PKD, a phorbol ester and diacylglycerol-stimulated serine protein kinase. The Journal of biological chemistry 157 7836415
2015 2-Deoxy-d-Glucose Ameliorates PKD Progression. Journal of the American Society of Nephrology : JASN 153 26534924
2020 Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review. Lipids in health and disease 152 32466765
2007 Dimeric PKD regulates membrane fission to form transport carriers at the TGN. The Journal of cell biology 123 18086912
2002 Archaeal surface layer proteins contain beta propeller, PKD, and beta helix domains and are related to metazoan cell surface proteins. Structure (London, England : 1993) 120 12377130
1996 Protein kinase C mu (PKC mu) associates with the B cell antigen receptor complex and regulates lymphocyte signaling. Immunity 119 8885868
2005 PKCeta is required for beta1gamma2/beta3gamma2- and PKD-mediated transport to the cell surface and the organization of the Golgi apparatus. The Journal of cell biology 114 15824133
2001 Protein kinase C (PKC)eta-mediated PKC mu activation modulates ERK and JNK signal pathways. The Journal of biological chemistry 114 11741879
2003 EGF receptor tyrosine kinase inhibition attenuates the development of PKD in Han:SPRD rats. Kidney international 112 14531789
2011 PKD is a kinase of Vps34 that mediates ROS-induced autophagy downstream of DAPk. Cell death and differentiation 108 22095288
2000 Spatial and temporal regulation of protein kinase D (PKD). The EMBO journal 108 10856238
2011 Sour taste responses in mice lacking PKD channels. PloS one 100 21625513
2011 Hypoxia-inducible factor-1α (HIF-1α) and autophagy in polycystic kidney disease (PKD). American journal of physiology. Renal physiology 99 21270095
2011 PKD regulates membrane fission to generate TGN to cell surface transport carriers. Cold Spring Harbor perspectives in biology 91 21421913
2006 General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia. Development (Cambridge, England) 85 16943275
2011 The exocyst protein Sec10 interacts with Polycystin-2 and knockdown causes PKD-phenotypes. PLoS genetics 78 21490950
1999 Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor. The EMBO journal 78 10523301
2001 PKD in intestinal epithelial cells: rapid activation by phorbol esters, LPA, and angiotensin through PKC. American journal of physiology. Cell physiology 77 11245610
2012 Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation, episodic ataxia, and absences. Epilepsia 74 23126439
2002 Structural requirements for localization and activation of protein kinase C mu (PKC mu) at the Golgi compartment. The Journal of cell biology 73 11777941
2013 Pharmacologic reversion of epigenetic silencing of the PRKD1 promoter blocks breast tumor cell invasion and metastasis. Breast cancer research : BCR 68 23971832
1999 Dynamic re-distribution of protein kinase D (PKD) as revealed by a GFP-PKD fusion protein: dissociation from PKD activation. FEBS letters 66 10471840
2014 Melatonin promotes osteoblast differentiation and mineralization of MC3T3-E1 cells under hypoxic conditions through activation of PKD/p38 pathways. Journal of pineal research 62 25250639
2008 PKD, PKD2, and p38 MAPK mediate Hsp27 serine-82 phosphorylation induced by neurotensin in pancreatic cancer PANC-1 cells. Journal of cellular biochemistry 60 17570131
2017 Insulin Receptor and GPCR Crosstalk Stimulates YAP via PI3K and PKD in Pancreatic Cancer Cells. Molecular cancer research : MCR 59 28360038
2007 Phospholipase C beta3 is a key component in the Gbetagamma/PKCeta/PKD-mediated regulation of trans-Golgi network to plasma membrane transport. The Biochemical journal 59 17492941
2003 Combination treatment of PKD utilizing dual inhibition of EGF-receptor activity and ligand bioavailability. Kidney international 59 12969149
2013 PRRT2-related disorders: further PKD and ICCA cases and review of the literature. Journal of neurology 55 23299620
2013 Parallel analysis of mRNA and microRNA microarray profiles to explore functional regulatory patterns in polycystic kidney disease: using PKD/Mhm rat model. PloS one 55 23326503
2011 Inhibition of the P2X7 receptor reduces cystogenesis in PKD. Journal of the American Society of Nephrology : JASN 55 21636640
2006 Inhibition of HER-2(neu/ErbB2) restores normal function and structure to polycystic kidney disease (PKD) epithelia. Biochimica et biophysica acta 54 16797938
2013 Nerve injury induces glial cell line-derived neurotrophic factor (GDNF) expression in Schwann cells through purinergic signaling and the PKC-PKD pathway. Glia 53 23553603
2016 An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense. Cell reports 52 27184844
2010 Epidermal growth factor-mediated proliferation and sodium transport in normal and PKD epithelial cells. Biochimica et biophysica acta 52 20959142
1995 Protein kinase D (PKD): a novel target for diacylglycerol and phorbol esters. Mutation research 51 8538623
2019 Apoptosis and autophagy in polycystic kidney disease (PKD). Cellular signalling 50 31881325
2012 PKD controls αvβ3 integrin recycling and tumor cell invasive migration through its substrate Rabaptin-5. Developmental cell 50 22975325
2011 Design, Synthesis, and Biological Evaluation of PKD Inhibitors. Pharmaceutics 50 22267986
2007 PKD is recruited to sites of actin remodelling at the leading edge and negatively regulates cell migration. FEBS letters 50 17707375
2008 HNF-1beta regulates transcription of the PKD modifier gene Kif12. Journal of the American Society of Nephrology : JASN 48 19005009
2003 Involvement of PKCdelta and PKD in pulmonary microvascular endothelial cell hyperpermeability. American journal of physiology. Cell physiology 47 13679307
2017 Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells. Nutrients 46 28230729
2011 Lysophosphatidic acid suppresses endothelial cell CD36 expression and promotes angiogenesis via a PKD-1-dependent signaling pathway. Blood 44 21441463
2016 LPA/PKD-1-FoxO1 Signaling Axis Mediates Endothelial Cell CD36 Transcriptional Repression and Proangiogenic and Proarteriogenic Reprogramming. Arteriosclerosis, thrombosis, and vascular biology 42 27013613
2015 GPCR-mediated PLCβγ/PKCβ/PKD signaling pathway regulates the cofilin phosphatase slingshot 2 in neutrophil chemotaxis. Molecular biology of the cell 42 25568344
2010 VEGF stimulates PKD-mediated CREB-dependent orphan nuclear receptor Nurr1 expression: role in VEGF-induced angiogenesis. International journal of cancer 42 20715116
2006 Shuttling of HDAC5 in H9C2 cells regulates YY1 function through CaMKIV/PKD and PP2A. American journal of physiology. Cell physiology 42 16822951
2014 Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3. BMC structural biology 41 24998259
2011 βA3/A1-Crystallin controls anoikis-mediated cell death in astrocytes by modulating PI3K/AKT/mTOR and ERK survival pathways through the PKD/Bit1-signaling axis. Cell death & disease 40 21993393
2008 PKD prevents H2O2-induced apoptosis via NF-kappaB and p38 MAPK in RIE-1 cells. Biochemical and biophysical research communications 40 19059215
2018 A Rho signaling network links microtubules to PKD controlled carrier transport to focal adhesions. eLife 39 30028295
2017 Integrated field, laboratory, and theoretical study of PKD spread in a Swiss prealpine river. Proceedings of the National Academy of Sciences of the United States of America 39 29078391
2016 Biphasic Regulation of Yes-associated Protein (YAP) Cellular Localization, Phosphorylation, and Activity by G Protein-coupled Receptor Agonists in Intestinal Epithelial Cells: A NOVEL ROLE FOR PROTEIN KINASE D (PKD). The Journal of biological chemistry 39 27369082
2015 The cpk model of recessive PKD shows glutamine dependence associated with the production of the oncometabolite 2-hydroxyglutarate. American journal of physiology. Renal physiology 38 26155843
2008 Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts. Purinergic signalling 38 18438719
2005 What is the role of tubular epithelial cell apoptosis in polycystic kidney disease (PKD)? Cell cycle (Georgetown, Tex.) 38 16258272
2010 Activator of G protein signaling 3 promotes epithelial cell proliferation in PKD. Journal of the American Society of Nephrology : JASN 37 20488951
2018 A mutation affecting polycystin-1 mediated heterotrimeric G-protein signaling causes PKD. Human molecular genetics 36 29931260
2017 PKD knockdown inhibits pressure overload-induced cardiac hypertrophy by promoting autophagy via AKT/mTOR pathway. International journal of biological sciences 36 28367092
2008 Selective binding of phorbol esters and diacylglycerol by individual C1 domains of the PKD family. The Biochemical journal 36 18076381
2017 Kinobead and Single-Shot LC-MS Profiling Identifies Selective PKD Inhibitors. Journal of proteome research 35 28102076
2015 The PKD inhibitor CID755673 enhances cardiac function in diabetic db/db mice. PloS one 35 25798941
1996 Evidence that two phenotypically distinct mouse PKD mutations, bpk and jcpk, are allelic. Kidney international 34 8887273
2015 Positional mapping of PRKD1, NRP1 and PRDM1 as novel candidate disease genes in truncus arteriosus. Journal of medical genetics 33 25713110
2006 Transcriptome analysis of a rat PKD model: Importance of genes involved in extracellular matrix metabolism. Kidney international 32 16541020
2017 The PRKD1 E710D hotspot mutation is highly specific in separating polymorphous adenocarcinoma of the palate from adenoid cystic carcinoma and pleomorphic adenoma on FNA. Cancer cytopathology 30 29266837
2024 Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo. Cell stem cell 29 38181751
2022 PKD-dependent PARP12-catalyzed mono-ADP-ribosylation of Golgin-97 is required for E-cadherin transport from Golgi to plasma membrane. Proceedings of the National Academy of Sciences of the United States of America 29 34969853
2019 MEG3 can affect the proliferation and migration of colorectal cancer cells through regulating miR-376/PRKD1 axis. American journal of translational research 29 31632544
2017 Diet-induced obesity links to ER positive breast cancer progression via LPA/PKD-1-CD36 signaling-mediated microvascular remodeling. Oncotarget 29 28186980
2012 PKD controls mitotic Golgi complex fragmentation through a Raf-MEK1 pathway. Molecular biology of the cell 29 23242995
2005 Expression of the protein kinase D (PKD) family during mouse embryogenesis. Gene expression patterns : GEP 29 16377259
2017 Identification and Expression Analysis of the Complete Family of Zebrafish pkd Genes. Frontiers in cell and developmental biology 28 28271061
2011 Ginsenoside Rh2(S) induces the differentiation and mineralization of osteoblastic MC3T3-E1 cells through activation of PKD and p38 MAPK pathways. BMB reports 28 22026999
2006 Regulation of type II PIP kinase by PKD phosphorylation. Cellular signalling 28 16563698
2021 A PKD-MFF signaling axis couples mitochondrial fission to mitotic progression. Cell reports 27 34010649
2009 A Golgi PKD activity reporter reveals a crucial role of PKD in nocodazole-induced Golgi dispersal. Traffic (Copenhagen, Denmark) 26 19416469
2006 pKD: re-designing protein pKa values. Nucleic acids research 26 16845054
2014 Novel mutations of PKD genes in the Czech population with autosomal dominant polycystic kidney disease. BMC medical genetics 25 24694054
2013 The PKD domain distinguishes the trafficking and amyloidogenic properties of the pigment cell protein PMEL and its homologue GPNMB. Pigment cell & melanoma research 25 23452376
2019 Twist1-Induced Epithelial Dissemination Requires Prkd1 Signaling. Cancer research 24 31676574
2011 Differential PKC-dependent and -independent PKD activation by G protein α subunits of the Gq family: selective stimulation of PKD Ser⁷⁴⁸ autophosphorylation by Gαq. Cellular signalling 23 22227248
2020 A high-throughput screening platform for Polycystic Kidney Disease (PKD) drug repurposing utilizing murine and human ADPKD cells. Scientific reports 21 32144367
2016 Lack of PRKD2 and PRKD3 kinase domain somatic mutations in PRKD1 wild-type classic polymorphous low-grade adenocarcinomas of the salivary gland. Histopathology 21 26426580
2015 Molecular cloning, epigenetic regulation, and functional characterization of Prkd1 gene promoter in dopaminergic cell culture models of Parkinson's disease. Journal of neurochemistry 21 26230914
2008 Rapid and quantitative DNA analysis of genetic mutations for polycystic kidney disease (PKD) using magnetic/luminescent nanoparticles. Analytical and bioanalytical chemistry 21 18256809
2008 Identification of genes involved in the ciliary trafficking of C. elegans PKD-2. Developmental dynamics : an official publication of the American Association of Anatomists 21 18407554
2023 Multiple pkd and piezo gene family members are required for atrioventricular valve formation. Nature communications 20 36639367
2002 PKD: a new protein kinase C-dependent pathway in platelets. Blood 20 12393506

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