Affinage

PRKD2

Serine/threonine-protein kinase D2 · UniProt Q9BZL6

Round 2 corrected
Length
878 aa
Mass
96.7 kDa
Annotated
2026-04-28
130 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRKD2 is a diacylglycerol- and phorbol ester-activated serine/threonine kinase that integrates lipid-dependent signals into diverse cellular processes including vesicular trafficking, cell migration, immune cell differentiation, and metabolic homeostasis. Its catalytic activity is governed by PKCη-mediated phosphorylation of activation-loop residues Ser706/Ser710, while CK1δ/ε phosphorylation at Ser244 controls nuclear retention by blocking CRM-1-dependent export, enabling nuclear substrates such as HDAC7 and Bcl6 to be phosphorylated (PMID:17962809, PMID:31980486). PRKD2 directly phosphorylates HSP27 at Ser82 downstream of VEGF and neurotensin to promote endothelial cell migration and angiogenesis, participates in β1-integrin recycling via the Rab5c–AMAP1–PRKD2 complex during cancer cell invasion, and restrains T follicular helper cell differentiation through cytoplasmic sequestration of Bcl6 (PMID:18440775, PMID:22734003, PMID:31980486). In pancreatic β-cells, PRKD2 limits L-type Ca²⁺ channel expression and activity to restrain insulin secretion, and its loss causes hyperinsulinemia preceding insulin resistance (PMID:29789568).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2000 High

    Identification of PRKD2 as a DAG/phorbol ester-responsive kinase with a distinctive domain architecture established the existence of a second PKD family member and defined its activation mechanism through autophosphorylation at Ser876.

    Evidence Recombinant expression, phorbol ester binding, mutagenesis of Ser876, histone H1 kinase assay, CCK-B receptor activation in AGS-B cells

    PMID:11062248

    Open questions at the time
    • Endogenous substrates beyond histone H1 were unknown
    • Activation-loop phosphorylation sites and upstream kinases not yet defined
    • Tissue expression pattern and isoform-specific functions not resolved
  2. 2004 High

    Two parallel advances defined PRKD2 as a TGN-resident kinase required for basolateral protein sorting and as a Bcr-Abl substrate that drives NF-κB activation in CML cells, revealing both a housekeeping trafficking role and an oncogenic signaling axis.

    Evidence Kinase-dead PRKD2 TGN localization and basolateral sorting assay in MDCK cells; Bcr-Abl phosphorylation of the PH domain, phosphomimetic mutants, and NF-κB reporter in LAMA84 cells

    PMID:14743217 PMID:15604256

    Open questions at the time
    • Direct TGN substrates of PRKD2 not identified
    • Tyrosine phosphorylation site(s) in PH domain not mapped to specific residues
    • Whether NF-κB activation requires kinase activity or is solely PH-domain-mediated was unclear
  3. 2007 High

    The upstream regulatory logic controlling PRKD2 nuclear accumulation was decoded: PKCη phosphorylates the activation loop (Ser706/Ser710) for catalytic activation while CK1δ/ε phosphorylates Ser244 to block CRM-1-dependent nuclear export, enabling PRKD2 to phosphorylate the nuclear substrate HDAC7 and induce Nur77.

    Evidence Phospho-specific antibodies, site-directed mutagenesis, CK1δ/ε kinase assay, CRM-1 co-IP, HDAC7 phosphorylation and Nur77 reporter in CCK2R-stimulated cells

    PMID:17962809

    Open questions at the time
    • Whether other nuclear substrates are regulated by the same retention mechanism was untested
    • Structural basis for CRM-1 binding and its disruption by Ser244 phosphorylation unknown
  4. 2008 High

    Direct phosphorylation of HSP27 at Ser82 by PRKD2 was established as a p38 MAPK-independent effector arm downstream of both VEGF (endothelial) and neurotensin (pancreatic cancer) signaling, linking PRKD2 to angiogenesis and cell migration.

    Evidence In vitro kinase assay with recombinant PKD and HSP27, siRNA in HUVECs and PANC-1 cells, p38 inhibitor controls, tubulogenesis and migration assays

    PMID:17570131 PMID:18440775

    Open questions at the time
    • Whether PRKD2 phosphorylates HSP27 in all cell types or context-specifically was unresolved
    • Structural determinants of HSP27 recognition by PRKD2 unknown
  5. 2009 Medium

    PRKD2 was positioned as the dominant PKD isoform in monocytes, required for lysophosphatidylcholine-induced ERK/p38 MAPK activation and chemotactic migration, extending its role to inflammatory lipid signaling.

    Evidence siRNA and dominant-negative PRKD2 in THP-1 monocytes, ERK/p38 phosphorylation and transwell migration assays

    PMID:19520973

    Open questions at the time
    • Direct substrate connecting PRKD2 to ERK/p38 activation not identified
    • In vivo relevance in atherosclerosis or inflammation not tested
  6. 2012 High

    The Rab5c–AMAP1–PRKD2 complex was shown to control β1-integrin recycling to the plasma membrane during EGF-driven breast cancer invasion, providing a molecular mechanism for PRKD2's role in integrin trafficking.

    Evidence Reciprocal Co-IP, GST pulldown establishing direct AMAP1–PRKD2 binding, siRNA of each component, integrin recycling and Matrigel invasion assays

    PMID:22734003

    Open questions at the time
    • Whether PRKD2 kinase activity is required for complex formation or only for downstream signaling was not fully distinguished
    • Cargo specificity beyond β1 integrin not explored
  7. 2014 High

    HSP90 was identified as a PRKD2 chaperone whose inhibition triggers proteasomal degradation of PRKD2, connecting PRKD2 protein stability to hypoxia-induced HIF-1α accumulation and VEGF-A-driven tumor angiogenesis.

    Evidence Co-IP of HSP90–PRKD2, proteasome inhibitor rescue, ectopic PRKD2 restoration of HIF-1α/VEGF-A, in vivo tumor angiogenesis

    PMID:25297628

    Open questions at the time
    • Direct mechanism by which PRKD2 stabilizes or induces HIF-1α not established
    • Whether HSP90 chaperoning is isoform-specific to PRKD2 vs. PKD1/PKD3 unknown
  8. 2018 High

    A physiological role for PRKD2 in metabolic homeostasis was established: PRKD2 knockout in mice causes hyperinsulinemia through derepression of L-type Ca²⁺ channel expression/activity in β-cells, with a naturally occurring primate nonsense mutation providing cross-species validation.

    Evidence PRKD2-KO mouse, patch-clamp electrophysiology, Ca²⁺ imaging, insulin secretion assays, rhesus K410X mutation

    PMID:29789568

    Open questions at the time
    • Direct substrate or transcriptional target through which PRKD2 suppresses L-type channel expression not identified
    • Contribution of PRKD2 kinase activity versus scaffolding to the β-cell phenotype unresolved
  9. 2020 High

    PRKD2 was shown to phosphorylate and cytoplasmically sequester Bcl6, forming a mutually inhibitory feedback loop that restrains T follicular helper cell differentiation and germinal center responses.

    Evidence Prkd2-null and ENU mutant mice, Co-IP and phosphorylation assay of PRKD2–Bcl6, nuclear/cytoplasmic fractionation, flow cytometry of TFH/GC cells

    PMID:31980486

    Open questions at the time
    • Specific Bcl6 phosphorylation site(s) targeted by PRKD2 not mapped
    • Whether the PRKD2–Bcl6 axis operates in other lymphocyte subsets (e.g., B cells) unknown
  10. 2022 Medium

    PRKD2 expression was linked to epitranscriptomic regulation, with METTL3-mediated m6A modification destabilizing PRKD2 mRNA in skeletal muscle; elevated PRKD2 promotes GLUT4 expression and AKT-dependent glucose uptake.

    Evidence m6A-seq, METTL3 overexpression/knockdown, PRKD2 siRNA rescue, glucose uptake and GLUT4/p-AKT Western blot, HFD mouse model

    PMID:36058761

    Open questions at the time
    • Direct mechanism connecting PRKD2 kinase activity to GLUT4 transcription or translocation not established
    • Whether PRKD2 phosphorylates AKT pathway components directly or acts indirectly is unknown
    • Single-study finding; independent replication needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full substrate repertoire of PRKD2, structural basis for isoform-specific functions relative to PKD1/PKD3, the mechanism by which PRKD2 suppresses L-type Ca²⁺ channel expression, and whether the PRKD2–Bcl6 axis has therapeutic implications in autoimmunity.
  • No phosphoproteomics-based substrate screen published for PRKD2
  • No crystal or cryo-EM structure of PRKD2
  • Isoform-specific versus redundant functions with PKD1/PKD3 systematically undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 4 GO:0008289 lipid binding 1
Localization
GO:0031410 cytoplasmic vesicle 2 GO:0005634 nucleus 1 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1430728 Metabolism 2 R-HSA-168256 Immune System 2
Partners
AMAP1BCL6BCR-ABL1HDAC7HSP27HSP90AA1KIDINS220RAB5C
Complex memberships
Rab5c–AMAP1–PRKD2 integrin recycling complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 PRKD2 (protein kinase D2) was identified as a novel serine/threonine kinase with two N-terminal cysteine-rich zinc finger motifs, a pleckstrin homology (PH) domain, and a catalytic domain. Phorbol ester (PDBu) binding to PRKD2 and diacylglycerol-dependent autophosphorylation were demonstrated in vivo. Ser876 in the C-terminus was identified as an in vivo phosphorylation site correlating with kinase activation. Gastrin acting via the CCK-B receptor was shown to be a physiological activator of PRKD2 in AGS-B cells, and activated PRKD2 phosphorylated exogenous substrate histone H1. Recombinant protein expression, in vivo phorbol ester binding assay, autophosphorylation assay, site-directed mutagenesis, exogenous substrate (histone H1) kinase assay, stable transfection with CCK-B receptor The Journal of biological chemistry High 11062248
2004 PRKD2 is the predominant PKD family isoform expressed in Bcr-Abl+ chronic myeloid leukemia cells and is a substrate of Bcr-Abl. Bcr-Abl tyrosine-phosphorylates PRKD2 in its pleckstrin homology (PH) domain. A phosphomimetic mutant of PRKD2 at the PH domain activates NF-κB independently of PRKD2 catalytic activity, and Bcr-Abl-induced NF-κB activation in LAMA84 cells is largely mediated by tyrosine-phosphorylated PRKD2. Immunoprecipitation, Western blot with phospho-specific antibodies, dominant-negative and phosphomimetic mutants, NF-κB reporter assay, siRNA knockdown Cancer research High 15604256
2004 Kinase-inactive forms of PKD2 (PRKD2) localize to the trans-Golgi network (TGN) along with PKD1 and PKD3. PKD activity is specifically required for basolateral sorting of membrane proteins from the TGN in polarized epithelial cells, with different isoforms (PKD1, PKD2, PKD3) each contributing to this process in a cargo-specific manner. Dominant-negative (kinase-dead) PKD isoform overexpression, immunofluorescence localization to TGN, basolateral vs. apical protein trafficking assays in polarized MDCK cells Nature cell biology Medium 14743217
2007 PRKD2 nuclear accumulation is controlled by three phosphorylation events downstream of CCK2 receptor activation: (1) phosphorylation at Ser706 and Ser710 in the activation loop by PKCη, conferring catalytic activity; and (2) phosphorylation at Ser244 within the zinc-finger domain by CK1δ/ε, which blocks nuclear export by preventing interaction with the CRM-1 export machinery. Only nuclear, active PRKD2 efficiently phosphorylates the nuclear substrate HDAC7, leading to Nur77 expression. Phospho-specific antibodies, site-directed mutagenesis of Ser244/Ser706/Ser710, CK1δ/ε overexpression and kinase assays, CRM-1 co-immunoprecipitation, HDAC7 phosphorylation assay, Nur77 reporter assay, nuclear fractionation The EMBO journal High 17962809
2007 PKD1 and PRKD2 (PKD2 kinase isoform) co-exist with neurotensin (NT)-containing vesicles in BON endocrine cells. PRKD2 (along with PKD1) phosphorylates Kidins220, which localizes to NT vesicles and is required for NT secretion. Overexpression of kinase-dead PKD1 abolishes Kidins220 expression and NT vesicle formation, placing PRKD2 and PKD1 in a pathway regulating hormone secretion. Co-immunoprecipitation, confocal immunofluorescence, siRNA knockdown of PKD1 and PRKD2, kinase-dead PKD1 overexpression, NT secretion assay The Journal of biological chemistry Medium 18048355
2008 In pancreatic cancer PANC-1 cells, neurotensin induces Hsp27 Ser82 phosphorylation through convergent PKC/PRKD2- and p38 MAPK-dependent pathways. Knockdown of PRKD2 (alone or combined with PKD1 siRNA) significantly reduces neurotensin-stimulated Hsp27 Ser82 phosphorylation, and combined knockdown virtually abolishes it, demonstrating that PRKD2 is a direct upstream regulator of Hsp27 phosphorylation independently of p38 MAPK. siRNA knockdown of PRKD2 (multiple targeting sequences), PKD overexpression, phospho-specific Hsp27 Ser82 Western blot, p38 MAPK inhibitor (SB202190), PKC inhibitor (GF-I) Journal of cellular biochemistry Medium 17570131
2008 VEGF activates PRKD2 via PKC in human umbilical vein endothelial cells (HUVECs). Activated PRKD2 directly phosphorylates HSP27 at Ser82 in vitro and in HUVECs, independently of p38 kinase. siRNA-mediated knockdown of PKD1 and PRKD2 inhibits VEGF-induced HUVEC migration and tubulogenesis, establishing PRKD2 as a mediator of the angiogenic response to VEGF. siRNA knockdown of PRKD2 and PKD1, in vitro kinase assay with recombinant PKD and HSP27, phospho-specific Ser82 antibody, p38 inhibitor (SB203580), HUVEC migration and tubulogenesis assays Cellular signalling High 18440775
2009 PRKD2 is the predominant PKD isoform expressed in monocytic THP-1 cells and primary human monocytes. Lysophosphatidylcholine (lysoPC) induces rapid PKD2 activation. Using dominant-negative mutants and siRNA, PRKD2 was shown to be required for lysoPC-induced activation of both ERK and p38 MAPK, and the PRKD2→p38 pathway specifically controls lysoPC-induced monocyte migration. siRNA knockdown, dominant-negative PRKD2 overexpression, ERK/p38 phosphorylation assays, transwell monocyte migration assay Arteriosclerosis, thrombosis, and vascular biology Medium 19520973
2011 IFN-γ induces expression of both PD-L1 and PRKD2 in human oral squamous carcinoma Tca8113 cells. PRKD2 knockdown (shRNA/siRNA) or pharmacological PKD inhibition significantly reduces IFN-γ-induced PD-L1 surface expression, and consequently decreases CD8+ T-cell apoptosis mediated by the PD-1/PD-L1 pathway, identifying PRKD2 as a regulator of IFN-γ-induced PD-L1 expression in tumor cells. shRNA/siRNA knockdown of PRKD2, flow cytometry for PD-L1 surface expression, PKD chemical inhibitor, CD8+ T-cell apoptosis assay, in vivo tumor model Immunobiology Medium 22204817
2012 Rab5c promotes formation of an AMAP1–PRKD2 complex that facilitates recycling of β1 integrins (e.g., α3β1) to the plasma membrane during EGF-stimulated breast cancer cell invasion. AMAP1 directly binds PRKD2 and links to the cytoplasmic tail of the β1 integrin subunit. GTP-Rab5c binds AMAP1, and EGF-induced activation of Rab5c is required to promote intracellular AMAP1–PRKD2 association and consequent integrin recycling. Co-immunoprecipitation, GST pulldown, siRNA knockdown of AMAP1/PRKD2/Rab5c, cell invasion assays, fluorescence microscopy of integrin recycling The Journal of cell biology High 22734003
2013 The ETS transcription factor GABP (GABPα) is required for PRKD2 expression in hematopoietic stem cells (HSCs). Deletion of Gabpa markedly reduces Prkd2 mRNA and protein levels. Reduced PRKD2 expression decreases HSC cell cycle entry, and ectopic PRKD2 rescues proliferation of Gabpα-null BCR-ABL-expressing cells, placing PRKD2 downstream of GABP in the pathway controlling HSC cycling and CML development. Conditional Gabpa knockout mice, bioinformatic promoter analysis, RT-PCR/Western blot, PRKD2 overexpression rescue, pharmacological PKD inhibition, cell-cycle analysis Proceedings of the National Academy of Sciences of the United States of America Medium 23345428
2014 HSP90 binds to and stabilizes PRKD2 protein in human cancer cells. Pharmacological HSP90 inhibition triggers proteasome-dependent degradation of PRKD2. PRKD2 is essential for hypoxia-induced accumulation of HIF-1α and NF-κB activation in tumor cells, and ectopic PRKD2 expression partially restores HIF-1α levels and secreted VEGF-A after HSP90 inhibition, demonstrating that PRKD2 connects HSP90 and hypoxia signaling to NF-κB/VEGF-A-driven tumor angiogenesis. Co-immunoprecipitation of HSP90–PRKD2, proteasome inhibitor rescue experiments, ectopic PRKD2 overexpression, HIF-1α and NF-κB reporter/Western blot assays, in vivo tumor angiogenesis models Cancer research High 25297628
2018 PRKD2 deficiency in mice (PRKD2-KO) causes hyperinsulinemia that precedes insulin resistance and metabolic disorders. Mechanistically, PRKD2 deletion increases expression and activity of L-type Ca2+ channels in pancreatic β-cells, augmenting high-glucose- and depolarization-induced Ca2+ influx and thereby promoting excessive insulin secretion. PRKD2-KO mouse model, glucose tolerance tests, patch-clamp electrophysiology of β-cells, L-type Ca2+ channel expression (Western blot), Ca2+ imaging, insulin secretion assays; validated by a naturally occurring K410X nonsense mutation in rhesus monkeys Nature communications High 29789568
2020 PRKD2 directly binds Bcl6 and phosphorylates Bcl6 in a PRKD2-dependent manner, constraining Bcl6 to the cytoplasm and thereby limiting T follicular helper (TFH) cell differentiation. In the absence of PRKD2, Bcl6 undergoes unrestricted nuclear translocation, causing excessive TFH development, germinal center expansion, and hypergammaglobulinemia. During immunization, Bcl6 reciprocally represses PRKD2 expression in CD4+ T cells, forming a mutually inhibitory feedback loop that stabilizes TFH commitment. Prkd2 targeted null mice, forward genetic ENU screen, Co-immunoprecipitation of PRKD2–Bcl6, phosphorylation assay, Bcl6 nuclear/cytoplasmic fractionation, flow cytometry of TFH/GC cells, serum immunoglobulin quantification Science immunology High 31980486
2006 Overexpression of wild-type PRKD2 in BON carcinoid cells significantly increases cell proliferation and invasion compared to kinase-dead PRKD2 or vector controls, while siRNA-mediated PRKD2 inhibition decreases proliferation and invasion, demonstrating that PRKD2 catalytic activity is required for these oncogenic phenotypes. Stable transfection of wild-type vs. kinase-dead PRKD2, siRNA knockdown, cell proliferation assay, Matrigel invasion assay Biochemical and biophysical research communications Medium 16899224
2011 PRKD2 (PKD2 kinase) overexpression in AGS gastric adenocarcinoma cells enhances cell proliferation, migration, and colony formation relative to PKD1-overexpressing or vector control cells, indicating divergent roles for PKD1 and PRKD2 in gastric tumor biology and that elevated PRKD2 promotes an invasive tumor phenotype. Stable transfection of PKD1 or PRKD2, MTT and proliferation assays, scratch migration assay, Transwell invasion assay, clonogenic assay, Western blot Experimental oncology Medium 22217708
2022 In skeletal muscle, METTL3-mediated m6A modification of PRKD2 mRNA reduces its stability and expression. Quercetin decreases METTL3 and m6A levels on PRKD2 mRNA, increasing PRKD2 protein expression. Elevated PRKD2 promotes GLUT4 expression and p-AKT signaling to enhance glucose uptake and reduce insulin resistance; PRKD2 silencing reverses quercetin's protective effects, placing PRKD2 downstream of METTL3-mediated epitranscriptomic regulation in the insulin-signaling pathway. m6A-seq/bioinformatics for m6A site prediction, METTL3 overexpression/knockdown, PRKD2 siRNA knockdown, mRNA stability assay, glucose uptake assay, Western blot for GLUT4/p-AKT, in vivo HFD mouse model Nutrition, metabolism, and cardiovascular diseases Medium 36058761

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature genetics 1382 19430480
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
1996 PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science (New York, N.Y.) 1172 8650545
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1997 PKD1 interacts with PKD2 through a probable coiled-coil domain. Nature genetics 560 9171830
1999 Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet (London, England) 447 10023895
1998 Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell 445 9568711
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2011 Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature 405 22020285
2000 Cardiac defects and renal failure in mice with targeted mutations in Pkd2. Nature genetics 302 10615132
2008 A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia. Nature genetics 294 18758461
1999 Identification and characterization of polycystin-2, the PKD2 gene product. The Journal of biological chemistry 286 10497221
1999 Specific association of the gene product of PKD2 with the TRPC1 channel. Proceedings of the National Academy of Sciences of the United States of America 260 10097141
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
2004 Functional proteomics mapping of a human signaling pathway. Genome research 247 15231748
2001 The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway. Current biology : CB 247 11553327
2018 Structure of the human PKD1-PKD2 complex. Science (New York, N.Y.) 214 30093605
2016 The Structure of the Polycystic Kidney Disease Channel PKD2 in Lipid Nanodiscs. Cell 211 27768895
2004 Protein kinase D regulates basolateral membrane protein exit from trans-Golgi network. Nature cell biology 208 14743217
2015 A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 198 26673895
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2000 Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome research 161 11042152
2000 The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton. Proceedings of the National Academy of Sciences of the United States of America 160 10760273
2000 Molecular cloning and characterization of the human protein kinase D2. A novel member of the protein kinase D family of serine threonine kinases. The Journal of biological chemistry 159 11062248
2007 Function and dynamics of PKD2 in Chlamydomonas reinhardtii flagella. The Journal of cell biology 153 17984324
2011 Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2. Development (Cambridge, England) 145 21307093
1999 Somatic PKD2 mutations in individual kidney and liver cysts support a "two-hit" model of cystogenesis in type 2 autosomal dominant polycystic kidney disease. Journal of the American Society of Nephrology : JASN 145 10405208
2012 Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. Human mutation 144 22508176
2011 Interferon-γ-induced PD-L1 surface expression on human oral squamous carcinoma via PKD2 signal pathway. Immunobiology 134 22204817
2007 Zebrafish curly up encodes a Pkd2 ortholog that restricts left-side-specific expression of southpaw. Development (Cambridge, England) 120 17360770
2004 Protein kinase D1 phosphorylates HDAC7 and induces its nuclear export after T-cell receptor activation. The Journal of biological chemistry 118 15623513
2003 PKD2 cation channel is required for directional sperm movement and male fertility. Current biology : CB 117 14680633
2010 The ADPKD genes pkd1a/b and pkd2 regulate extracellular matrix formation. Disease models & mechanisms 116 20335443
2019 Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes & development 110 31753913
2002 Trans-heterozygous Pkd1 and Pkd2 mutations modify expression of polycystic kidney disease. Human molecular genetics 108 12140187
2011 Pkd1l1 complexes with Pkd2 on motile cilia and functions to establish the left-right axis. Development (Cambridge, England) 105 21307098
2007 Zebrafish mutations affecting cilia motility share similar cystic phenotypes and suggest a mechanism of cyst formation that differs from pkd2 morphants. Developmental biology 104 18178183
2006 Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry. Molecular & cellular proteomics : MCP 96 17192257
2005 Global phosphoproteome of HT-29 human colon adenocarcinoma cells. Journal of proteome research 91 16083285
2012 Rab5c promotes AMAP1-PRKD2 complex formation to enhance β1 integrin recycling in EGF-induced cancer invasion. The Journal of cell biology 90 22734003
2020 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. Molecular cell 88 32707033
2016 The TRP Channels Pkd2, NompC, and Trpm Act in Cold-Sensing Neurons to Mediate Unique Aversive Behaviors to Noxious Cold in Drosophila. Current biology : CB 87 27818173
2004 PKD2 interacts and co-localizes with mDia1 to mitotic spindles of dividing cells: role of mDia1 IN PKD2 localization to mitotic spindles. The Journal of biological chemistry 87 15123714
1999 Germinal and somatic mutations in the PKD2 gene of renal cysts in autosomal dominant polycystic kidney disease. Human molecular genetics 84 9949210
2010 Nuclear import of histone deacetylase 5 by requisite nuclear localization signal phosphorylation. Molecular & cellular proteomics : MCP 83 21081666
1997 Characterization of the exon structure of the polycystic kidney disease 2 gene (PKD2). Genomics 82 9286709
1997 A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2). American journal of human genetics 77 9326320
2004 Protein kinase D2 mediates activation of nuclear factor kappaB by Bcr-Abl in Bcr-Abl+ human myeloid leukemia cells. Cancer research 75 15604256
2010 Pkd1 and Pkd2 are required for normal placental development. PloS one 73 20862291
2008 Vascular endothelial growth factor induces heat shock protein (HSP) 27 serine 82 phosphorylation and endothelial tubulogenesis via protein kinase D and independent of p38 kinase. Cellular signalling 72 18440775
1999 Aberrant splicing in the PKD2 gene as a cause of polycystic kidney disease. Journal of the American Society of Nephrology : JASN 71 10541293
2015 Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease. Journal of the American Society of Nephrology : JASN 69 26139440
2009 Conditional mutation of Pkd2 causes cystogenesis and upregulates beta-catenin. Journal of the American Society of Nephrology : JASN 67 19939939
2008 Cyst formation in kidney via B-Raf signaling in the PKD2 transgenic mice. The Journal of biological chemistry 67 19098310
2014 Diagnosis of autosomal dominant polycystic kidney disease using efficient PKD1 and PKD2 targeted next-generation sequencing. Molecular genetics & genomic medicine 60 25333066
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
1999 Genes homologous to the autosomal dominant polycystic kidney disease genes (PKD1 and PKD2). European journal of human genetics : EJHG 60 10602361
2022 PKD1 and PKD2 mRNA cis-inhibition drives polycystic kidney disease progression. Nature communications 57 35965273
2009 Novel method for genomic analysis of PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease. Human mutation 55 18837007
2002 Molecular basis of polycystic kidney disease: PKD1, PKD2 and PKHD1. Current opinion in nephrology and hypertension 55 11981261
1999 Cellular activation triggered by the autosomal dominant polycystic kidney disease gene product PKD2. Molecular and cellular biology 55 10207066
2000 Location of mutations within the PKD2 gene influences clinical outcome. Kidney international 54 10760080
2014 HSP90 supports tumor growth and angiogenesis through PRKD2 protein stabilization. Cancer research 52 25297628
2007 VEGF receptor inhibition blocks liver cyst growth in pkd2(WS25/-) mice. American journal of physiology. Cell physiology 50 17475663
2019 circ-PKD2 inhibits carcinogenesis via the miR-204-3p/APC2 axis in oral squamous cell carcinoma. Molecular carcinogenesis 49 31206208
2015 Mechanosensory Genes Pkd1 and Pkd2 Contribute to the Planar Polarization of Brain Ventricular Epithelium. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 26245976
1996 An Italian family with autosomal dominant polycystic kidney disease unlinked to either the PKD1 or PKD2 gene. American journal of kidney diseases : the official journal of the National Kidney Foundation 46 9158217
2020 Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure. eLife 45 32364494
2016 Pancreatic Cysts in Autosomal Dominant Polycystic Kidney Disease: Prevalence and Association with PKD2 Gene Mutations. Radiology 44 27046073
2016 Atypical calcium regulation of the PKD2-L1 polycystin ion channel. eLife 44 27348301
2009 Lysophosphatidylcholine activates a novel PKD2-mediated signaling pathway that controls monocyte migration. Arteriosclerosis, thrombosis, and vascular biology 44 19520973
2018 Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure. eLife 43 30511640
1998 A spectrum of mutations in the polycystic kidney disease-2 (PKD2) gene from eight Canadian kindreds. Journal of the American Society of Nephrology : JASN 43 9773786
2014 Osteoblast-specific deletion of Pkd2 leads to low-turnover osteopenia and reduced bone marrow adiposity. PloS one 42 25464512
2008 Centrosome overduplication and mitotic instability in PKD2 transgenic lines. Cell biology international 42 18725310
2007 Phosphorylation at Ser244 by CK1 determines nuclear localization and substrate targeting of PKD2. The EMBO journal 41 17962809
2011 Association of PKD2 (polycystin 2) mutations with left-right laterality defects. American journal of kidney diseases : the official journal of the National Kidney Foundation 38 21719175
1997 Novel stop and frameshifting mutations in the autosomal dominant polycystic kidney disease 2 (PKD2) gene. Human genetics 37 9402976
2014 An mTOR anti-sense oligonucleotide decreases polycystic kidney disease in mice with a targeted mutation in Pkd2. Human molecular genetics 36 24847003
2001 Mutations of the human polycystic kidney disease 2 (PKD2) gene. Human mutation 35 11438989
2020 PKD2/polycystin-2 induces autophagy by forming a complex with BECN1. Autophagy 34 32543276
2010 Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 34 21115670
2020 Chlamydomonas PKD2 organizes mastigonemes, hair-like glycoprotein polymers on cilia. The Journal of cell biology 33 32348466
2018 The Value of Genetic Testing in Polycystic Kidney Diseases Illustrated by a Family With PKD2 and COL4A1 Mutations. American journal of kidney diseases : the official journal of the National Kidney Foundation 33 29395486
2007 Overexpression of PKD2 in the mouse is associated with renal tubulopathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 33 18048422
2011 CaMK-II is a PKD2 target that promotes pronephric kidney development and stabilizes cilia. Development (Cambridge, England) 31 21752935
2007 PKD1, PKD2, and their substrate Kidins220 regulate neurotensin secretion in the BON human endocrine cell line. The Journal of biological chemistry 31 18048355
1997 Molecular cloning, cDNA sequence analysis, and chromosomal localization of mouse Pkd2. Genomics 31 9339380
2016 Technical Evaluation: Identification of Pathogenic Mutations in PKD1 and PKD2 in Patients with Autosomal Dominant Polycystic Kidney Disease by Next-Generation Sequencing and Use of a Comprehensive New Classification System. PloS one 30 27835667
2019 SUMO1 modification of PKD2 channels regulates arterial contractility. Proceedings of the National Academy of Sciences of the United States of America 29 31822608
2021 Detection of PKD1 and PKD2 Somatic Variants in Autosomal Dominant Polycystic Kidney Cyst Epithelial Cells by Whole-Genome Sequencing. Journal of the American Society of Nephrology : JASN 28 34716216
2014 Antisense-mediated angiotensinogen inhibition slows polycystic kidney disease in mice with a targeted mutation in Pkd2. American journal of physiology. Renal physiology 28 25537744
2022 Circ-PKD2 promotes Atg13-mediated autophagy by inhibiting miR-646 to increase the sensitivity of cisplatin in oral squamous cell carcinomas. Cell death & disease 26 35220397
2022 Quercetin ameliorated insulin resistance via regulating METTL3-mediated N6-methyladenosine modification of PRKD2 mRNA in skeletal muscle and C2C12 myocyte cell line. Nutrition, metabolism, and cardiovascular diseases : NMCD 26 36058761
2018 Deficiency of PRKD2 triggers hyperinsulinemia and metabolic disorders. Nature communications 25 29789568
2008 Co-inheritance of a PKD1 mutation and homozygous PKD2 variant: a potential modifier in autosomal dominant polycystic kidney disease. European journal of clinical investigation 25 18257781
2013 GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2. Proceedings of the National Academy of Sciences of the United States of America 24 23345428
1999 Seven novel mutations of the PKD2 gene in families with autosomal dominant polycystic kidney disease. Kidney international 24 10411676
2018 Novel Mutations in the PKD1 and PKD2 Genes of Chinese Patients with Autosomal Dominant Polycystic Kidney Disease. Kidney & blood pressure research 23 29529603
2014 Role of PKD2 in rheotaxis in Dictyostelium. PloS one 23 24520414
1999 The rat pkd2 protein assumes distinct subcellular distributions in different organs. The American journal of physiology 23 10600939
2014 Loss-of-function RNAi screens in breast cancer cells identify AURKB, PLK1, PIK3R1, MAPK12, PRKD2, and PTK6 as sensitizing targets of rapamycin activity. Cancer letters 22 25193464
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 Identification of novel PKD1 and PKD2 mutations in a Chinese population with autosomal dominant polycystic kidney disease. Scientific reports 21 26632257
1998 A novel frameshift mutation induced by an adenosine insertion in the polycystic kidney disease 2 (PKD2) gene. Kidney international 21 9573526
2022 PKD2 founder mutation is the most common mutation of polycystic kidney disease in Taiwan. NPJ genomic medicine 19 35778421
2020 Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation. Science immunology 19 31980486
2011 Differential expression of PKD1 and PKD2 in gastric cancer and analysis of PKD1 and PKD2 function in the model system. Experimental oncology 19 22217708
2006 Overexpression of wild-type PKD2 leads to increased proliferation and invasion of BON endocrine cells. Biochemical and biophysical research communications 19 16899224
2022 Membrane stretching activates calcium permeability of a putative channel Pkd2 during fission yeast cytokinesis. Molecular biology of the cell 18 36200871
2015 Human polycystin-2 transgene dose-dependently rescues ADPKD phenotypes in Pkd2 mutant mice. The American journal of pathology 18 26435415
2011 High Resolution Melt analysis for mutation screening in PKD1 and PKD2. BMC nephrology 18 22008521
2020 A high throughput zebrafish chemical screen reveals ALK5 and non-canonical androgen signalling as modulators of the pkd2-/- phenotype. Scientific reports 17 31919453
2012 The Drosophila TRPP cation channel, PKD2 and Dmel/Ced-12 act in genetically distinct pathways during apoptotic cell clearance. PloS one 17 22347485
2012 Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes. International urology and nephrology 16 22367170
2018 Truncating PKHD1 and PKD2 mutations alter energy metabolism. American journal of physiology. Renal physiology 15 30566001
2014 Identification of novel PKD1 and PKD2 mutations in Korean patients with autosomal dominant polycystic kidney disease. BMC medical genetics 15 25491204
2009 Phenylephrine induces elevated RhoA activation and smooth muscle alpha-actin expression in Pkd2+/- vascular smooth muscle cells. Hypertension research : official journal of the Japanese Society of Hypertension 15 19893564
2012 Clinical utility of PKD2 mutation testing in a polycystic kidney disease cohort attending a specialist nephrology out-patient clinic. BMC nephrology 14 22863349
2007 Distinct protein domains regulate ciliary targeting and function of C. elegans PKD-2. Experimental cell research 13 18037411
1998 Characterization of the murine polycystic kidney disease (Pkd2) gene. Mammalian genome : official journal of the International Mammalian Genome Society 13 9716661