Affinage

PIKFYVE

1-phosphatidylinositol 3-phosphate 5-kinase · UniProt Q9Y2I7

Length
2098 aa
Mass
237.1 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIKfyve is a phosphoinositide kinase that phosphorylates PtdIns3P to generate PI(3,5)P2 and PtdIns to generate PI(5)P, serving as the master regulator of endolysosomal membrane identity, fission/fusion balance, and cargo trafficking. It operates within a stoichiometrically defined ternary complex (5 Vac14 : 1 PIKfyve : 1 Fig4) in which Vac14 scaffolds and stimulates PIKfyve activity, PIKfyve autophosphorylation represses its own kinase while activating Fig4 phosphatase, and Fig4 acts as both a PI(3,5)P2 phosphatase and a protein phosphatase that dephosphorylates PIKfyve to restore kinase activity (PMID:10419465, PMID:33098764, PMID:17556371). PIKfyve is recruited to endosomal membranes via FYVE-domain binding to VPS34-derived PtdIns3P, and its activity is modulated by PKB/AKT (Ser318), AMPK (Ser307), and ULK1 (Ser1548) phosphorylation in response to insulin, contraction, and glucose starvation, respectively, as well as by palmitoylation via zDHHC9/zDHHC21 that controls protein stability (PMID:11706043, PMID:15546921, PMID:23905686, PMID:34107300, PMID:34291577). Through its lipid products, PIKfyve governs phagosome/lysosome maturation, MVB biogenesis, GLUT4 and integrin recycling, selective mTORC1–TFEB signaling, autophagy flux, exosome secretion, and innate immune responses including TLR trafficking and type I IFN production (PMID:14551253, PMID:25041080, PMID:35040777, PMID:35020443, PMID:34107300, PMID:27438886, PMID:24600036).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    The fundamental question of what lipid kinase activity PIKfyve possesses was resolved: it synthesizes both PtdIns5P and PtdIns(3,5)P2 in vitro with striking substrate specificity, establishing it as a dual-specificity phosphoinositide kinase.

    Evidence In vitro kinase assay with recombinant protein and HPLC product identification in COS cells

    PMID:10419465

    Open questions at the time
    • No in vivo lipid measurements
    • Relative contribution of each product to cellular signaling unknown
    • Structural basis of substrate specificity unresolved
  2. 2001 High

    How PIKfyve reaches its site of action was established: the FYVE domain binds PtdIns3P on late endosomal membranes and is essential for membrane targeting, while kinase-dead PIKfyve causes dominant vacuolation demonstrating that active PIKfyve is required for endomembrane homeostasis.

    Evidence PtdIns3P liposome binding, FYVE domain mutagenesis, kinase-dead mutant expression with fluorescence microscopy and rescue in multiple cell types

    PMID:11285266 PMID:11706043

    Open questions at the time
    • Whether additional membrane-targeting determinants beyond FYVE domain exist in vivo
    • Mechanism by which kinase loss leads to vacuolation not resolved
  3. 2003 High

    The cellular functions of PIKfyve were delineated: it selectively regulates fluid-phase endocytosis, MVB morphogenesis, and late endosome-to-TGN retrograde transport—but not transferrin recycling or EGF receptor degradation—establishing pathway specificity.

    Evidence Stable inducible kinase-dead lines, fluid-phase marker uptake, electron microscopy, yeast two-hybrid identification of Rab9 effector p40 interaction

    PMID:14530284 PMID:14551253

    Open questions at the time
    • How PIKfyve achieves pathway specificity unclear
    • Relationship between p40 phosphorylation and retrograde transport not fully resolved
  4. 2004 High

    Signal-dependent regulation of PIKfyve was discovered: PKB/AKT phosphorylates Ser318 in response to insulin, stimulating kinase activity and modulating GLUT4 vesicle trafficking; simultaneously, Vac14/ArPIKfyve was identified as a required positive regulator and physical partner.

    Evidence In vitro PKB kinase assay, phospho-specific antibodies, S318A mutant in 3T3-L1 adipocytes; Co-IP, siRNA knockdown of Vac14 with in vitro kinase and HPLC readouts

    PMID:15542851 PMID:15546921

    Open questions at the time
    • Whether other kinases phosphorylate Ser318 in non-insulin contexts
    • How Vac14 stimulates PIKfyve enzymatic activity mechanistically
  5. 2007 High

    The ternary PIKfyve–ArPIKfyve–Sac3 (PAS) complex was reconstituted, revealing that Sac3/Fig4 preferentially hydrolyzes PI(3,5)P2 and that balanced kinase/phosphatase activities within the complex control endosomal carrier vesicle formation.

    Evidence Co-IP, co-fractionation, in vitro phosphatase assay, siRNA, in vitro vesicle formation reconstitution

    PMID:17556371

    Open questions at the time
    • Stoichiometry of the complex unknown at this stage
    • How Sac3 integrates into complex architecture unresolved
  6. 2009 High

    The cpn60/TCP1 domain of PIKfyve was identified as the key interaction module mediating both ArPIKfyve–Sac3 binding and the p40/JLP adapter interaction, and PIKfyve was shown to control lysosomal degradation of CaV1.2 channels in neurons, extending its substrates beyond canonical endosomal cargo.

    Evidence Systematic domain mutagenesis in triple-transfected cells; NMDA-dependent CaV1.2 co-IP, siRNA with excitotoxicity readout; JLP yeast two-hybrid and cargo-specific trafficking assays

    PMID:19056739 PMID:19840946 PMID:19841139

    Open questions at the time
    • Whether cpn60_TCP1 domain interactions are mutually exclusive or simultaneous
    • How NMDA signaling activates PIKfyve
  7. 2012 High

    In vivo, PIKfyve was confirmed as the sole source of PI(3,5)P2 and the predominant source of PI5P (generated indirectly via 3-phosphatase action on PI(3,5)P2); functionally, PtdIns5P and PI(3,5)P2 were shown to be dissociable, with PI5P mediating actin remodeling and PI(3,5)P2 driving vacuolation.

    Evidence Pikfyve hypomorph mouse, shRNA, quantitative tissue phosphoinositide mass measurements; differential-dose YM201636 with HPLC and actin/GLUT4 assays

    PMID:22621786 PMID:23047693

    Open questions at the time
    • Identity of the 3-phosphatase converting PI(3,5)P2 to PI5P in vivo
    • Tissue-specific regulation of each lipid product
  8. 2013 High

    Two additional upstream kinases—AKT (EGF-stimulated EGFR-to-lysosome routing) and AMPK (Ser307, contraction-stimulated glucose uptake)—were shown to directly phosphorylate and activate PIKfyve, establishing it as a signaling hub integrating growth factor and energy-sensing inputs.

    Evidence In vitro AKT/AMPK kinase assays, phosphomutants, receptor trafficking, glucose uptake in muscle

    PMID:23757022 PMID:23905686

    Open questions at the time
    • Cross-talk between Ser307 and Ser318 phosphorylation events
    • Whether other metabolic kinases also regulate PIKfyve
  9. 2014 High

    PIKfyve was established as essential for phagosome maturation (PtdIns3P-to-PI(3,5)P2 conversion, LAMP1/cathepsin acquisition) and for endolysosomal TLR-induced type I IFN production (via ATF3 transcriptional repression), linking it to innate immunity.

    Evidence Multiple PIKfyve inhibitors in macrophage phagocytosis; pharmacological/genetic inactivation with ATF3/IFN promoter ChIP; TLR9/AP-3 trafficking assays

    PMID:24600036 PMID:25041080 PMID:25170925

    Open questions at the time
    • How PI(3,5)P2 mechanistically promotes PtdIns3P removal on phagosomes
    • Whether ATF3 induction is a direct consequence of PI(3,5)P2 depletion or lysosome stress
  10. 2016 High

    The cellular consequences of PIKfyve loss were refined: lysosome enlargement results from coalescence (fusion over fission) rather than biosynthesis; PIKfyve inhibition increases exosome secretion via impaired MVB–lysosome fusion; the downstream effector TRPML1 was identified as a key mediator of vacuole resolution and nutrient recovery.

    Evidence Live fusion/fission dynamics imaging, TFEB/TFE3 knockout, quantitative EM and MS of exosomal fractions, TRPML1 genetic manipulation and starvation survival assays

    PMID:27438886 PMID:27623384 PMID:29661845

    Open questions at the time
    • Whether TRPML1 is the sole PI(3,5)P2 effector for fission
    • How PI(3,5)P2 regulates the balance between exosomal release and degradation
  11. 2020 High

    Cryo-EM resolved the PAS complex architecture at 5 Vac14 : 1 PIKfyve : 1 Fig4 stoichiometry and revealed a self-regulatory circuit: PIKfyve autophosphorylation represses its kinase and stimulates Fig4 phosphatase, while Fig4 acts as a protein phosphatase on PIKfyve to restore kinase activity; sterically, PIKfyve cannot reach membrane-embedded substrates within the complex.

    Evidence Cryo-EM structure, in vitro phosphatase/kinase reconstitution, mutagenesis

    PMID:33098764

    Open questions at the time
    • How the complex is remodeled to allow membrane access in vivo
    • How Vac14 pentamerization is regulated
  12. 2021 High

    A third upstream kinase, ULK1 (activated by AMPK during glucose starvation), was shown to phosphorylate PIKfyve Ser1548, selectively increasing PI5P (not PI(3,5)P2) synthesis and promoting PI5P-containing autophagosome formation, thereby linking PIKfyve to autophagy initiation.

    Evidence In vitro ULK1 kinase assay, S1548D phosphomimetic, quantitative phosphoinositide measurements, autophagy flux assays

    PMID:34107300

    Open questions at the time
    • Structural basis for how Ser1548 phosphorylation shifts product specificity
    • Whether PI5P on autophagosomes recruits specific effectors
  13. 2021 High

    PIKfyve stability was shown to be controlled by palmitoylation by zDHHC9/zDHHC21; prion infection or UPR disrupts acyltransferase topology causing PIKfyve deacylation, degradation, and endolysosomal hypertrophy—a disease-relevant post-translational control mechanism.

    Evidence Acylation assays, zDHHC knockdown/overexpression, mouse and organotypic brain slice prion infection models, PI(3,5)P2 rescue

    PMID:34291577

    Open questions at the time
    • Which palmitoylation site(s) on PIKfyve are critical
    • Whether deacylation is an active regulatory mechanism beyond disease contexts
  14. 2022 Medium

    The mechanism by which PIKfyve controls TFEB nuclear translocation was resolved: PI(3,5)P2 is required for mTORC1 to access TFEB (but not other substrates) at the lysosome, and PP2A (not calcineurin) dephosphorylates TFEB-Ser211 when PIKfyve is inhibited; separately, PIKfyve was shown to govern Retriever/CCC-mediated integrin recycling downstream of VPS34.

    Evidence mTORC1 substrate profiling, PP2A/calcineurin inhibitors, TFEB nuclear localization; endogenous co-localization, PIKfyve inhibition Retriever displacement, integrin recycling, VPS34 epistasis

    PMID:35020443 PMID:35040777

    Open questions at the time
    • How PI(3,5)P2 physically mediates mTORC1–TFEB proximity
    • Whether PP2A regulation is TFEB-specific or extends to other TFE family members
    • How PIKfyve products recruit Retriever to endosomes

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) how the PIKfyve-Vac14-Fig4 complex is conformationally rearranged to allow PIKfyve access to membrane substrates in vivo; (2) the structural basis for phosphorylation-dependent switching between PI(3,5)P2 and PI5P product specificity; (3) the identity and regulation of the 3-phosphatase generating PI5P from PI(3,5)P2 in vivo; and (4) how tissue- and context-specific PIKfyve regulation is achieved.
  • Membrane access mechanism for the intact PAS complex
  • Product specificity switching mechanism
  • In vivo 3-phosphatase identity
  • Tissue-specific regulatory mechanisms

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0140096 catalytic activity, acting on a protein 2 GO:0008289 lipid binding 1
Localization
GO:0005764 lysosome 4 GO:0005768 endosome 4 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-9609507 Protein localization 2 R-HSA-9612973 Autophagy 2
Partners
FIG4JLPP40TRPML1VAC14VPS34
Complex memberships
PIKfyve-Vac14-Fig4 (PAS complex)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PIKfyve (p235) is a mammalian lipid kinase that synthesizes PtdIns5P and PtdIns(3,5)P2 in vitro, displaying striking specificity for PtdIns over PI substrates; deletion mutant analysis showed that regions beyond the predicted catalytic domain are critical for enzymatic activity. In vitro kinase assay with recombinant protein expressed in COS cells, HPLC analysis of lipid products, deletion mutant analysis The Journal of biological chemistry High 10419465
2001 PIKfyve enzymatic activity is required for mammalian cell morphology and endomembrane homeostasis; kinase-dead PIKfyve(K1831E) causes dominant vacuolation of endosomal origin, and disruption of the FYVE-domain localization signal abolishes this phenotype, indicating that active PIKfyve at late endocytic membranes is essential. Dominant-negative kinase-dead mutant expression, fluorescence microscopy, cell viability assays, rescue with wild-type PIKfyve The Journal of biological chemistry High 11285266
2001 PIKfyve localizes to late endocytic membranes via its FYVE domain binding to PtdIns3P; the FYVE domain is absolutely required for endosomal membrane targeting, and wortmannin treatment dissociates PIKfyve from endosomes; an additional low-affinity PtdIns3P-binding site exists in the catalytic domain. PtdIns3P liposome binding assays, FYVE domain mutagenesis, wortmannin treatment, fluorescence microscopy The Journal of biological chemistry High 11706043
2002 PIKfyve is responsible for PtdIns5P biosynthesis in cellular contexts; expression of PIKfyve(WT) increases intracellular PtdIns5P, while dominant-negative PIKfyve(K1831E) decreases it; PtdIns5P levels decrease under hypo-osmotic stress, linking PIKfyve to the osmotic response pathway. 32P-labeling, HPLC head-group analysis, in vitro type II PIP kinase conversion assay, dominant-negative expression in multiple cell types The Journal of biological chemistry High 12270933
2003 PIKfyve selectively regulates fluid-phase endocytosis and multivesicular body morphogenesis; kinase-dead PIKfyve impairs late uptake of horseradish peroxidase and disrupts MVB morphology (fewer internal vesicles), without affecting transferrin recycling, EGF receptor degradation, or cathepsin D sorting. Stable inducible cell lines, fluid-phase marker uptake, confocal microscopy with organelle markers, electron microscopy Molecular biology of the cell High 14551253
2003 PIKfyve physically interacts with the Rab9 effector p40 via its chaperonin domain; enzymatically active PIKfyve promotes membrane attachment of p40 and phosphorylates it on serine residues, facilitating late endosome-to-TGN transport. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, differential centrifugation, in vitro kinase assay, phosphoserine antibody The Journal of biological chemistry High 14530284
2004 PKB/Akt phosphorylates PIKfyve on Ser318, stimulating its PtdIns3P 5-kinase activity; this phosphorylation occurs in intact cells in response to insulin in a PI3K-dependent manner; overexpression of PIKfyve[S318A] in adipocytes enhances insulin-stimulated IRAP/GLUT4 vesicle translocation. In vitro kinase assay, phospho-specific antibodies, 3T3-L1 adipocyte translocation assay, site-directed mutagenesis Journal of cell science High 15546921
2004 Human Vac14 (ArPIKfyve) is a positive regulator of PIKfyve enzymatic activity; it co-fractionates and co-localizes with PIKfyve, physically associates with it, and its siRNA-mediated knockdown reduces PIKfyve kinase activity and PtdIns(3,5)P2 production, causing endomembrane vacuolation. Co-immunoprecipitation, siRNA knockdown, in vitro kinase assay, 32P-labeling/HPLC, confocal microscopy Molecular and cellular biology High 15542851
2006 PIKfyve is predominantly associated with early endosomal tubular and vesicular elements and regulates endosome-to-TGN retrograde transport; siRNA suppression of PIKfyve causes swollen endosomal structures and a clear defect in retrograde trafficking without affecting EGF receptor degradation or transferrin recycling. Live and fixed cell imaging, siRNA knockdown, receptor trafficking assays in HeLa cells Journal of cell science High 16954148
2007 Sac3 (mammalian Fig4) forms a stable ternary complex with ArPIKfyve and PIKfyve; Sac3 preferentially hydrolyzes PtdIns(3,5)P2 in vitro; siRNA knockdown of Sac3 elevates PtdIns(3,5)P2 levels; reconstitution assays show Sac3 loss gains function in carrier vesicle formation while PIKfyve or ArPIKfyve depletion causes loss of function. Co-immunoprecipitation, co-fractionation, in vitro phosphatase assay, siRNA knockdown, 32P-labeling, in vitro vesicle formation reconstitution The Journal of biological chemistry High 17556371
2007 PIKfyve mediates HB-EGF-stimulated EGFR nuclear trafficking and EGFR binding to the cyclin D1 promoter; PIKfyve was identified as part of EGFR immune complexes by mass spectrometry, and siRNA silencing of PIKfyve blocks EGFR nuclear translocation and cell cycle progression. Mass spectrometry of EGFR immune complexes, siRNA knockdown, nuclear fractionation, chromatin immunoprecipitation Cancer research Medium 17909029
2008 YM201636, a potent selective inhibitor of PIKfyve, blocks PtdIns(3,5)P2 production, causes accumulation of late endosomal compartments, and blocks retroviral budding; specificity confirmed by siRNA against PIKfyve and rescue with drug-resistant yeast Fab1 ortholog. Small-molecule inhibitor, siRNA knockdown, rescue with yeast Fab1, phosphoinositide measurements, cell biology assays EMBO reports High 18188180
2008 PIKfyve interacts with the kinesin adapter JLP via the PIKfyve cpn60_TCP1 domain; both proteins are required for microtubule-based endosome-to-TGN transport of furin but not microtubule-independent Tac-TGN38 delivery. Yeast two-hybrid, pulldown, co-immunoprecipitation, siRNA knockdown, cargo trafficking assay, microinjection of interacting peptides The Journal of biological chemistry High 19056739
2009 PIKfyve-containing PAS complex: Sac3 assembled within the PIKfyve-ArPIKfyve-Sac3 core retains active PtdIns(3,5)P2 phosphatase activity; the cpn60_TCP1 domain of PIKfyve mediates ArPIKfyve-Sac3 subcomplex binding; kinase and phosphatase activities do not affect complex stability. Truncation and point mutants of all three proteins in triple-transfected COS cells, vacuolation assay as functional readout, biochemical binding analysis The Journal of biological chemistry High 19840946
2009 PIKfyve regulates lysosomal targeting and degradation of voltage-gated Ca2+ channel CaV1.2; NMDA receptor activation recruits PIKfyve to CaV1.2 channels, increases PtdIns(3,5)P2, and promotes CaV1.2 targeting to lysosomes; PIKfyve knockdown prevents CaV1.2 degradation and increases neuronal susceptibility to excitotoxicity. Co-immunoprecipitation, siRNA knockdown, live imaging, neuronal excitotoxicity assays, PtdIns(3,5)P2 measurements The Journal of cell biology High 19841139
2009 PIKfyve stimulates EAAT2 glutamate transporter activity and increases its membrane abundance; the effect requires Ser318 in the SGK1 phosphorylation consensus of PIKfyve, as S318A mutant abolishes PIKfyve's stimulatory effect. Xenopus oocyte expression, electrophysiology, confocal microscopy, site-directed mutagenesis (S318A) Cellular physiology and biochemistry Medium 19910676
2010 PIKfyve is required for macropinosome-to-late endosome/lysosome fusion; disruption of PIKfyve (by interfering mutant, siRNA, or pharmacological inhibition) inhibits intracellular replication of Salmonella by blocking SCV maturation and SPI2-T3SS engagement. Dominant-negative mutant, siRNA, pharmacological inhibition, 4D videomicroscopy, Salmonella infection assay The EMBO journal High 20300065
2012 In vivo, Pikfyve generates all of the PI(3,5)P2 pool and is also responsible for nearly all PI5P production, with PI5P generated directly from PI(3,5)P2 likely via 3'-phosphatase activity; demonstrated using a Pikfyve hypomorph mouse and shRNA silencing of residual transcript. Mouse hypomorph (gene trap), shRNA silencing in fibroblasts, phosphoinositide mass measurement in tissues Proceedings of the National Academy of Sciences of the United States of America High 23047693
2012 PIKfyve-synthesized PtdIns5P mediates insulin-induced actin stress fiber disassembly, while PtdIns(3,5)P2 is responsible for cellular vacuolation; these two lipid products are functionally dissociable using differential dosing of YM201636. Differential-dose PIKfyve inhibitor (YM201636), HPLC phosphoinositide measurement, actin stress fiber imaging, GLUT4 translocation assay American journal of physiology. Cell physiology Medium 22621786
2012 PtdIns5P produced via PIKfyve and MTMR3 promotes cell migration; PIKfyve and MTMR3 constitute a phosphoinositide loop generating PtdIns5P via PtdIns(3,5)P2; exogenous PtdIns5P or bacterial PtdIns5P-producing enzyme directly stimulates migration. siRNA screen, migration assays in tissue culture and Drosophila in vivo model, exogenous PtdIns5P addition, bacterial enzyme EMBO reports High 23154468
2013 AKT phosphorylates and activates PIKfyve upon EGF stimulation, promoting vesicle trafficking of EGFR to lysosomes for degradation; in AKT-impaired cells EGFR accumulates in early endosomes with prolonged ERK/RSK signaling; similar regulation occurs for PDGFR. Kinase assay, phospho-specific antibodies, AKT inhibition, PIKfyve siRNA, receptor trafficking assays, dominant-negative approaches Science signaling High 23757022
2013 AMPK phosphorylates PIKfyve at Ser307, promoting its translocation to endosomal membranes and PtdIns(3,5)P2 synthesis; this is required for contraction/AMPK-stimulated glucose uptake in skeletal muscle. In vitro AMPK kinase assay, S307A mutant, subcellular fractionation, siRNA knockdown in myotubes, glucose uptake assay in muscle The Biochemical journal High 23905686
2014 PIKfyve inhibition blocks phagosome maturation in macrophages by delaying PtdIns3P removal and reducing acquisition of LAMP1 and cathepsin D on phagosomes, impairing degradative capacity without affecting acidification. PIKfyve pharmacological inhibitors, FcγR-mediated phagocytosis assay, live imaging, immunofluorescence with lysosomal markers, degradation assays Traffic (Copenhagen, Denmark) High 25041080
2014 PIKfyve is required for endolysosomal TLR-induced type I IFN production; PIKfyve inactivation induces expression of the transcriptional repressor ATF3, which binds the IFN promoter and blocks transcription; this is independent of receptor/ligand trafficking. PIKfyve pharmacological inhibition and genetic inactivation, ATF3 expression analysis, IFN promoter binding assay, chromatin IP Journal of immunology Medium 24600036
2015 APP (amyloid precursor protein) directly binds Vac14 via its intracellular domain and associates with the PIKfyve complex (Vac14/PIKfyve/Fig4); APP binding drives formation of PI(3,5)P2-positive vesicles; APP family members are required for PIKfyve function; PIKfyve complex is required for APP trafficking. Proteo-liposome interactome assay, GST pulldown with purified Vac14, co-immunoprecipitation, C. elegans genetic epistasis, PI(3,5)P2 vesicle formation assay Cellular and molecular life sciences High 26216398
2016 PIKfyve inhibition increases exosome secretion and induces secretory autophagy by impairing fusion of lysosomes with MVBs and autophagosomes; inhibition leads to more MVBs with more intraluminal vesicles and accumulation of autophagy proteins (LC3, p62, NBR1) in exosomal fractions. Apilimod treatment and siRNA, quantitative electron microscopy, mass spectrometry of exosomal fractions, density gradient fractionation, long-lived protein degradation assay Cellular and molecular life sciences High 27438886
2016 PIKfyve inhibition leads to lysosome enlargement primarily through lysosome coalescence (fusion over fission) rather than biosynthesis; PIKfyve inhibition activates TFEB/TFE3/MITF but this does not contribute to acute swelling; conditions reducing fusion curtail lysosome enlargement. Live imaging, organelle counting, fusion/fission dynamics analysis, TFEB/TFE3/MITF reporter assays, TFEB/TFE3 knockout Journal of cell science High 29661845
2016 PIKfyve regulates vacuole size and nutrient recovery during macropinocytosis, entosis, and phagocytosis through its downstream effector TRPML1 (cationic transporter); PIKfyve activity protects Ras-mutant cells from starvation-induced death. PIKfyve inhibitors, TRPML1 genetic manipulation, vacuole size measurement, nutrient recovery assay, starvation survival assay Developmental cell Medium 27623384
2017 Apilimod's cytotoxic activity is driven specifically by PIKfyve inhibition; a resistance mutation in the PIKfyve kinase domain confers apilimod resistance; a genome-wide CRISPR screen identified lysosomal genes and TFEB as determinants of apilimod sensitivity, supporting lysosome dysfunction as the major cytotoxic mechanism. Biochemical target validation, kinase domain resistance mutation, genome-wide CRISPR screen, siRNA knockdown Blood High 28104689
2017 PIKfyve is acylated by zDHHC9 and zDHHC21 acyltransferases; prion infection or UPR disturbs juxtavesicular acyltransferase topology causing PIKfyve deacylation, rapid degradation, and endolysosomal hypertrophy; overexpression of acyltransferases or PI(3,5)P2 supplementation suppresses prion-induced vacuolation. Acylation assay, zDHHC knockdown/overexpression, UPR induction, mouse/organotypic brain slice infection models, rescue with PI(3,5)P2 EMBO molecular medicine High 34291577
2017 PIKfyve coordinates neutrophil immune response through activation of Rac GTPase; PIKfyve inhibition blocks chemotaxis, ROS production, and Rac activation, while phagosome-lysosome fusion block can be partially rescued by TRPML1 agonists or Ca2+ ionophores. Human and mouse neutrophils, PIKfyve inhibitors, Rac activation assay, chemotaxis assay, ROS measurement, phagosome maturation assay, Ca2+ ionophore rescue Journal of immunology Medium 28779020
2018 PIKfyve promotes MHC class II antigen presentation by facilitating cathepsin S activity; PIKfyve inhibition delays phagosome-to-lysosome conversion and acidification, increases ROS, which reduces cathepsin S and B activity, impairing invariant chain processing and MHC class II presentation. PIKfyve inhibitors, cathepsin activity assay, phagosome maturation assay, novel bio-orthogonal antigen presentation assay, T cell activation assay iScience Medium 30612035
2020 The PIKfyve complex comprises five copies of Vac14 scaffolding protein and one copy each of PIKfyve kinase and Fig4 phosphatase; Fig4 is active as a lipid phosphatase within the complex while PIKfyve cannot access membrane-incorporated phosphoinositides due to steric constraints; PIKfyve autophosphorylation represses its lipid kinase activity and stimulates Fig4 phosphatase; Fig4 acts as a protein phosphatase on PIKfyve to stimulate its lipid kinase activity. Cryo-EM structure, structural-biochemical analysis, in vitro phosphatase and kinase assays, mutagenesis Molecular cell High 33098764
2020 Pharmacological inhibition of PIKfyve with apilimod or vacuolin-1 blocks content release and infection by VSV-ZEBOV and SARS-CoV-2 by interfering with late endosomal trafficking required for viral entry. Chimeric VSV with ebolavirus/SARS-CoV-2 envelope proteins, live SARS-CoV-2 infection assay, apilimod and vacuolin-1 treatment, content release imaging Proceedings of the National Academy of Sciences of the United States of America High 32764148
2021 ULK1 activated by AMPK during glucose starvation phosphorylates PIKfyve on Ser1548, increasing PIKfyve activity and PI(5)P synthesis (without changing PI(3,5)P2 levels); this promotes PI(5)P-containing autophagosome formation and autophagy flux. In vitro kinase assay (ULK1 phosphorylating PIKfyve), phosphomimetic S1548D mutant, phosphoinositide measurements, autophagy flux assays in multiple cell lines Developmental cell High 34107300
2021 PIKfyve inhibition activates an unconventional protein clearance mechanism involving exocytosis of aggregation-prone proteins, ameliorating ALS pathology in motor neurons from C9ORF72, TARDBP, FUS, and sporadic ALS models. Pharmacological PIKfyve inhibition, patient-derived iPSC motor neurons, ALS mouse models, exocytosis assays for aggregated proteins Cell Medium 36754049
2022 PIKfyve inhibition selectively blocks mTORC1-mediated phosphorylation of TFEB at Ser-211 without impairing mTORC1 activity toward other substrates; PI(3,5)P2 depletion prevents mTORC1 access to TFEB; PP2A (not calcineurin) dephosphorylates TFEB Ser-211 when PIKfyve is inhibited, enabling TFEB nuclear localization. mTORC1 substrate phosphorylation profiling, PP2A and calcineurin inhibitors, TFEB nuclear localization assay, mTORC1-TFEB interaction assay Molecular biology of the cell Medium 35020443
2022 PIKfyve and its upstream PI3-kinase VPS34 coordinate a phosphoinositide cascade to regulate Retriever-mediated recycling of integrins from endosomes; PIKfyve inhibition displaces Retriever and CCC complexes from endosomes; endogenous PIKfyve co-localizes with SNX17, Retriever, WASH, and CCC on endosomes. Co-localization of endogenous proteins, PIKfyve inhibition, Retriever/CCC displacement assay, integrin recycling assay, VPS34 epistasis eLife High 35040777
2023 PIKfyve is recruited to phagosomes and macropinosomes and PI(3,5)P2 accumulates 3 min after engulfment; PIKfyve activation stimulates its own dissociation from the membrane; retention of PI(3,5)P2 differs between phagosomes and macropinosomes indicating pathway-specific regulation. Novel PI(3,5)P2 reporter (SnxA), live imaging in Dictyostelium and mammalian cells, PIKfyve recruitment vs. activity dissection The Journal of cell biology Medium 37382666
2000 PIKfyve protein and enzymatic activity are found in cytosol (~76%), low-density microsomal fraction (~20%), and plasma membrane (~4%) of 3T3-L1 adipocytes; PIKfyve associates with TGN/MVB markers rather than recycling endosomes; insulin recruits cytosolic PIKfyve to intracellular membranes with a concomitant increase in lipid kinase activity. Subcellular fractionation, immunoadsorption, density gradient sedimentation, fluorescence microscopy, immunokinase assay The Journal of biological chemistry High 11112776
2001 PIKfyve physically associates with class IA PI3-kinase (p85/p110) in 3T3-L1 adipocytes; insulin specifically activates class IA PI3-K within PIKfyve immune complexes independently of IRS protein tyrosine phosphorylation. Co-immunoprecipitation, in vitro PI3K kinase assay in immune complexes, wortmannin/Triton sensitivity, insulin stimulation Molecular and cellular endocrinology Medium 11476939
2011 NPM-ALK tyrosine kinase physically associates with PIKfyve, activates its lipid kinase activity through tyrosine kinase activity (complex formation is kinase-independent), and PIKfyve promotes NPM-ALK-mediated cell invasion and MMP9 surface localization/maturation. Co-immunoprecipitation, PIKfyve lipid kinase assay, siRNA, YM201636 inhibition, invasion assay, immunofluorescence The Journal of biological chemistry Medium 21737449
2015 Class III PI3K (Vps34) is the main source of PtdIns3P for both PIKfyve enzymatic activity and membrane recruitment; Vps34 knockout in podocytes causes vacuolation through PIKfyve dysfunction, as PIKfyve overexpression rescues the vacuolation in PIKfyve-KO MEFs but not in Vps34-KO podocytes. Conditional Vps34 and Pikfyve knockout cells, HPLC phosphoinositide profiling, PtdIns3P biosensor, rescue experiments Biochimica et biophysica acta High 25619930
2015 PIKfyve activity is required for TLR9 trafficking to the LAMP1+ endosomal compartment for type I IFN signaling; PIKfyve inhibition blocks AP-3 recruitment to TLR9 endosomes while leaving VAMP3+ endosome trafficking intact. PIKfyve inhibitor treatment, confocal microscopy with TLR9/CpG/compartment markers, FLT3L-bone marrow DCs, RAW264.7 cells International immunology Medium 25170925
2019 PIKfyve activity is required for efficient V-ATPase and hydrolase delivery to phagosomes in Dictyostelium; PIKfyve-null cells fail to acidify phagosomes and cannot kill bacteria, making them more susceptible to Legionella infection. PIKfyve gene disruption in Dictyostelium, phagosome acidification assay, protease delivery assay, bacterial killing assay, Legionella infection PLoS pathogens High 30730983
2021 PIKfyve inhibition reduces tau aggregate trafficking into lysosomes and reduces tau seeding in neurons; PIKfyve functions downstream of Rac1 in the endocytic mechanism by which tau aggregates are internalized and routed to lysosomes. PIKfyve pharmacological inhibition, siRNA, Rac1 genetic manipulation, fluorescence-based tau seeding assay in neurons The Journal of biological chemistry Medium 33831417

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions. Journal of cell science 271 19889969
2008 A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding. EMBO reports 250 18188180
1985 Identification of two proteins (actin-binding protein and P235) that are hydrolyzed by endogenous Ca2+-dependent protease during platelet aggregation. The Journal of biological chemistry 230 2981831
1999 PIKfyve, a mammalian ortholog of yeast Fab1p lipid kinase, synthesizes 5-phosphoinositides. Effect of insulin. The Journal of biological chemistry 222 10419465
2006 The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde transport. Journal of cell science 220 16954148
2016 PIKfyve inhibition increases exosome release and induces secretory autophagy. Cellular and molecular life sciences : CMLS 217 27438886
2001 Mammalian cell morphology and endocytic membrane homeostasis require enzymatically active phosphoinositide 5-kinase PIKfyve. The Journal of biological chemistry 206 11285266
2012 In vivo, Pikfyve generates PI(3,5)P2, which serves as both a signaling lipid and the major precursor for PI5P. Proceedings of the National Academy of Sciences of the United States of America 195 23047693
2020 Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2. Proceedings of the National Academy of Sciences of the United States of America 166 32764148
2017 Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood 165 28104689
2009 Phosphatidylinositol 3,5-bisphosphate and Fab1p/PIKfyve underPPIn endo-lysosome function. The Biochemical journal 161 19272020
2007 Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex. The Journal of biological chemistry 159 17556371
2008 PIKfyve: Partners, significance, debates and paradoxes. Cell biology international 145 18304842
2011 The phosphoinositide kinase PIKfyve is vital in early embryonic development: preimplantation lethality of PIKfyve-/- embryos but normality of PIKfyve+/- mice. The Journal of biological chemistry 127 21349843
2004 Protein kinase B phosphorylation of PIKfyve regulates the trafficking of GLUT4 vesicles. Journal of cell science 113 15546921
2018 Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence. Journal of cell science 112 29661845
2006 The phosphoinositide kinase PIKfyve/Fab1p regulates terminal lysosome maturation in Caenorhabditis elegans. Molecular biology of the cell 110 16801682
2002 Phosphatidylinositol 5-phosphate biosynthesis is linked to PIKfyve and is involved in osmotic response pathway in mammalian cells. The Journal of biological chemistry 104 12270933
2019 A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt multiple events in lysosome homeostasis. Autophagy 102 30806145
2016 PIKfyve Regulates Vacuole Maturation and Nutrient Recovery following Engulfment. Developmental cell 102 27623384
2001 Phosphatidylinositol 3-phosphate-interacting domains in PIKfyve. Binding specificity and role in PIKfyve. Endomenbrane localization. The Journal of biological chemistry 97 11706043
2003 PIKfyve controls fluid phase endocytosis but not recycling/degradation of endocytosed receptors or sorting of procathepsin D by regulating multivesicular body morphogenesis. Molecular biology of the cell 96 14551253
1982 Purification and properties of human platelet P235. A high molecular weight protein substrate of endogenous calcium-activated protease(s). The Journal of biological chemistry 90 6177689
2014 PIKfyve inhibition interferes with phagosome and endosome maturation in macrophages. Traffic (Copenhagen, Denmark) 88 25041080
2013 AKT facilitates EGFR trafficking and degradation by phosphorylating and activating PIKfyve. Science signaling 87 23757022
2021 Autophagy Inhibition by Targeting PIKfyve Potentiates Response to Immune Checkpoint Blockade in Prostate Cancer. Nature cancer 84 34738088
2009 Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated phagocytosis. The Journal of cell biology 82 19153220
2023 PIKFYVE inhibition mitigates disease in models of diverse forms of ALS. Cell 78 36754049
2022 Roles of PIKfyve in multiple cellular pathways. Current opinion in cell biology 75 35584589
2010 Inhibition of the PtdIns(5) kinase PIKfyve disrupts intracellular replication of Salmonella. The EMBO journal 73 20300065
1986 Demonstration of a relationship between talin and P235, a major substrate of the calcium-dependent protease in platelets. Journal of cellular biochemistry 72 3009504
2020 Insights into Lysosomal PI(3,5)P2 Homeostasis from a Structural-Biochemical Analysis of the PIKfyve Lipid Kinase Complex. Molecular cell 69 33098764
2013 Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death. PloS one 69 23544129
2002 Requirement for PIKfyve enzymatic activity in acute and long-term insulin cellular effects. Endocrinology 68 12446602
2000 Localization and insulin-regulated relocation of phosphoinositide 5-kinase PIKfyve in 3T3-L1 adipocytes. The Journal of biological chemistry 68 11112776
2021 Glucose starvation induces autophagy via ULK1-mediated activation of PIKfyve in an AMPK-dependent manner. Developmental cell 67 34107300
2015 Daam2-PIP5K is a regulatory pathway for Wnt signaling and therapeutic target for remyelination in the CNS. Neuron 67 25754822
2012 Functional dissociation between PIKfyve-synthesized PtdIns5P and PtdIns(3,5)P2 by means of the PIKfyve inhibitor YM201636. American journal of physiology. Cell physiology 65 22621786
2012 NMDA receptor-mediated PIP5K activation to produce PI(4,5)P₂ is essential for AMPA receptor endocytosis during LTD. Neuron 63 22243752
2012 Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates cell migration. EMBO reports 63 23154468
2015 Phosphatidylinositol 3-Phosphate 5-Kinase, FAB1/PIKfyve Kinase Mediates Endosome Maturation to Establish Endosome-Cortical Microtubule Interaction in Arabidopsis. Plant physiology 56 26353760
2007 The phosphoinositide kinase PIKfyve mediates epidermal growth factor receptor trafficking to the nucleus. Cancer research 56 17909029
2003 Active PIKfyve associates with and promotes the membrane attachment of the late endosome-to-trans-Golgi network transport factor Rab9 effector p40. The Journal of biological chemistry 56 14530284
2019 Small molecule PIKfyve inhibitors as cancer therapeutics: Translational promises and limitations. Toxicology and applied pharmacology 55 31628917
2009 PIKfyve-ArPIKfyve-Sac3 core complex: contact sites and their consequence for Sac3 phosphatase activity and endocytic membrane homeostasis. The Journal of biological chemistry 55 19840946
2015 APP controls the formation of PI(3,5)P(2) vesicles through its binding of the PIKfyve complex. Cellular and molecular life sciences : CMLS 54 26216398
2011 Regulation of PIP5K activity by Arf6 and its physiological significance. Journal of cellular physiology 54 20945365
2009 YM201636, an inhibitor of retroviral budding and PIKfyve-catalyzed PtdIns(3,5)P2 synthesis, halts glucose entry by insulin in adipocytes. Biochemical and biophysical research communications 54 19289105
2013 Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle. The Biochemical journal 53 23905686
2006 Cloning and subcellular localization of a human phosphatidylinositol 3-phosphate 5-kinase, PIKfyve/Fab1. Gene 53 16448788
2004 A mammalian ortholog of Saccharomyces cerevisiae Vac14 that associates with and up-regulates PIKfyve phosphoinositide 5-kinase activity. Molecular and cellular biology 53 15542851
2009 PIKfyve regulates CaV1.2 degradation and prevents excitotoxic cell death. The Journal of cell biology 52 19841139
2004 Acquisition of unprecedented phosphatidylinositol 3,5-bisphosphate rise in hyperosmotically stressed 3T3-L1 adipocytes, mediated by ArPIKfyve-PIKfyve pathway. The Journal of biological chemistry 50 15546865
2009 Regulation of the glutamate transporter EAAT2 by PIKfyve. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 49 19910676
2007 ArPIKfyve-PIKfyve interaction and role in insulin-regulated GLUT4 translocation and glucose transport in 3T3-L1 adipocytes. Experimental cell research 48 17475247
2018 The Phosphoinositide Kinase PIKfyve Promotes Cathepsin-S-Mediated Major Histocompatibility Complex Class II Antigen Presentation. iScience 47 30612035
2016 Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition. FEBS letters 47 27135648
2012 PIKfyve and its Lipid products in health and in sickness. Current topics in microbiology and immunology 47 23086417
1991 Human platelet P-235, a talin-like actin binding protein, binds selectively to mixed lipid bilayers. Biochimica et biophysica acta 47 1900196
2022 Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes. eLife 43 35040777
2015 The Fab1/PIKfyve phosphoinositide phosphate kinase is not necessary to maintain the pH of lysosomes and of the yeast vacuole. The Journal of biological chemistry 42 25713145
2010 Rac controls PIP5K localisation and PtdIns(4,5)P₂ synthesis, which modulates vinculin localisation and neurite dynamics. Journal of cell science 41 20841379
2009 The beta- and gamma-isoforms of type I PIP5K regulate distinct stages of Ca2+ signaling in mast cells. Journal of cell science 41 19549683
2021 Synergistic Block of SARS-CoV-2 Infection by Combined Drug Inhibition of the Host Entry Factors PIKfyve Kinase and TMPRSS2 Protease. Journal of virology 39 34406858
2016 Active vacuolar H+ ATPase and functional cycle of Rab5 are required for the vacuolation defect triggered by PtdIns(3,5)P2 loss under PIKfyve or Vps34 deficiency. American journal of physiology. Cell physiology 39 27335171
2021 Loss of PIKfyve drives the spongiform degeneration in prion diseases. EMBO molecular medicine 38 34291577
2018 Inhibition of PIKfyve using YM201636 suppresses the growth of liver cancer via the induction of autophagy. Oncology reports 38 30569119
2014 PIKfyve, a class III lipid kinase, is required for TLR-induced type I IFN production via modulation of ATF3. Journal of immunology (Baltimore, Md. : 1950) 38 24600036
2010 Regulation of the glutamate transporter EAAT4 by PIKfyve. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 38 20110679
2023 A PI(3,5)P2 reporter reveals PIKfyve activity and dynamics on macropinosomes and phagosomes. The Journal of cell biology 36 37382666
2019 Biogenesis of lysosome-related organelles complex-1 (BORC) regulates late endosomal/lysosomal size through PIKfyve-dependent phosphatidylinositol-3,5-bisphosphate. Traffic (Copenhagen, Denmark) 36 31314175
2019 PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection. PLoS pathogens 33 30730983
2017 Inhibition of PIKfyve prevents myocardial apoptosis and hypertrophy through activation of SIRT3 in obese mice. EMBO molecular medicine 33 28396567
2009 Regulation of the Ca(2+) channel TRPV6 by the kinases SGK1, PKB/Akt, and PIKfyve. The Journal of membrane biology 33 20041238
2021 PIKfyve activity is required for lysosomal trafficking of tau aggregates and tau seeding. The Journal of biological chemistry 31 33831417
2019 Identification of PIKfyve kinase as a target in multiple myeloma. Haematologica 31 31582538
2018 Indolyl-Pyridinyl-Propenone-Induced Methuosis through the Inhibition of PIKFYVE. ACS omega 31 30221232
2017 The Lipid Kinase PIKfyve Coordinates the Neutrophil Immune Response through the Activation of the Rac GTPase. Journal of immunology (Baltimore, Md. : 1950) 31 28779020
2008 Kinesin adapter JLP links PIKfyve to microtubule-based endosome-to-trans-Golgi network traffic of furin. The Journal of biological chemistry 31 19056739
2022 PP2A-dependent TFEB activation is blocked by PIKfyve-induced mTORC1 activity. Molecular biology of the cell 30 35020443
2014 Plentiful PtdIns5P from scanty PtdIns(3,5)P2 or from ample PtdIns? PIKfyve-dependent models: Evidence and speculation (response to: DOI 10.1002/bies.201300012). BioEssays : news and reviews in molecular, cellular and developmental biology 30 25404370
2007 The phosphoinositide kinase PIP5K that produces the versatile signaling phospholipid PI4,5P(2). Biological & pharmaceutical bulletin 29 17827707
2021 Combined Inhibition of p38MAPK and PIKfyve Synergistically Disrupts Autophagy to Selectively Target Cancer Cells. Cancer research 28 33685990
2018 Apilimod, a candidate anticancer therapeutic, arrests not only PtdIns(3,5)P2 but also PtdIns5P synthesis by PIKfyve and induces bafilomycin A1-reversible aberrant endomembrane dilation. PloS one 28 30240452
2015 Class III PI 3-kinase is the main source of PtdIns3P substrate and membrane recruitment signal for PIKfyve constitutive function in podocyte endomembrane homeostasis. Biochimica et biophysica acta 28 25619930
2013 Muscle-specific Pikfyve gene disruption causes glucose intolerance, insulin resistance, adiposity, and hyperinsulinemia but not muscle fiber-type switching. American journal of physiology. Endocrinology and metabolism 28 23673157
2008 Elevated levels of PtdIns5P in NPM-ALK transformed cells: implication of PIKfyve. Biochemical and biophysical research communications 28 18501703
2025 Targeting PIKfyve-driven lipid metabolism in pancreatic cancer. Nature 27 40269157
2017 Deletion of PIKfyve alters alveolar macrophage populations and exacerbates allergic inflammation in mice. The EMBO journal 26 28533230
2016 The activation loop of PIP5K functions as a membrane sensor essential for lipid substrate processing. Science advances 26 28138522
2023 Targeting the lipid kinase PIKfyve upregulates surface expression of MHC class I to augment cancer immunotherapy. Proceedings of the National Academy of Sciences of the United States of America 25 38011559
2022 Disruption of PIKFYVE causes congenital cataract in human and zebrafish. eLife 25 35023829
2017 Identification of a conserved 8 aa insert in the PIP5K protein in the Saccharomycetaceae family of fungi and the molecular dynamics simulations and structural analysis to investigate its potential functional role. Proteins 24 28407364
2015 Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity. International immunology 24 25925170
2022 Membrane-mediated dimerization potentiates PIP5K lipid kinase activity. eLife 23 35976097
2001 Selective insulin-induced activation of class I(A) phosphoinositide 3-kinase in PIKfyve immune complexes from 3T3-L1 adipocytes. Molecular and cellular endocrinology 22 11476939
2023 PI4KA and PIKfyve: Essential phosphoinositide signaling enzymes involved in myriad human diseases. Current opinion in cell biology 21 37453227
2011 The nucleophosmin-anaplastic lymphoma kinase oncogene interacts, activates, and uses the kinase PIKfyve to increase invasiveness. The Journal of biological chemistry 21 21737449
2015 Shlnc-EC6 regulates murine erythroid enucleation by Rac1-PIP5K pathway. Development, growth & differentiation 20 26098172
2015 The Amyloid Precursor Protein Controls PIKfyve Function. PloS one 20 26125944