Affinage

PIK3R4

Phosphoinositide 3-kinase regulatory subunit 4 · UniProt Q99570

Length
1358 aa
Mass
153.1 kDa
Annotated
2026-04-28
100 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIK3R4 (VPS15/p150) is a serine/threonine protein kinase and essential regulatory subunit of class III phosphatidylinositol 3-kinase (PI3K-III) complexes that controls membrane trafficking, autophagy, and ciliogenesis. VPS15 forms a stable complex with VPS34, recruiting it to intracellular membranes and activating its lipid kinase activity to generate PI(3)P; this requires VPS15 autophosphorylation and an intact kinase domain, and is further regulated by Rab5 and Rab7 GTPases that direct the complex to early and late endosomes, respectively (PMID:8387919, PMID:12010460, PMID:14617358). ULK kinase phosphorylates VPS15 at multiple sites including S861, coupling autophagy initiation signals to VPS34 activation and autophagosome formation, while loss of VPS15 causes autophagic vacuolar myopathy, impaired lysosomal function, and defective neuronal migration through dysregulated Nischarin–Pak1 signaling (PMID:34121209, PMID:23630012, PMID:29311744). VPS15 also functions at the cis-Golgi in a VPS34-independent complex with GM130 to sort IFT20-dependent cargo to the primary cilium, and a human PIK3R4 missense mutation (R998Q) causes ciliopathy, cortical atrophy, and epilepsy (PMID:27882921, PMID:29311744).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1991 High

    Establishing that Vps15p is a protein kinase whose autophosphorylation and kinase activity are essential for vacuolar protein sorting and for its association with the PI3-kinase Vps34p answered how Vps34 lipid kinase activity is regulated upstream.

    Evidence Mutational analysis and in vivo phosphorylation assays in yeast

    PMID:1756716

    Open questions at the time
    • Substrate(s) of Vps15 kinase activity not identified
    • Whether Vps15 directly phosphorylates Vps34 remained unknown
  2. 1993 High

    Demonstrating that Vps15p and Vps34p form a stable membrane-associated complex, with Vps15p responsible for recruiting Vps34p to membranes, established the core architecture of the class III PI3K and explained how PI(3)P production is spatially controlled.

    Evidence Chemical cross-linking, native immunoprecipitation, sucrose gradient fractionation, and kinase assays in yeast

    PMID:7721937 PMID:8387919

    Open questions at the time
    • Structural basis of complex formation unresolved
    • Whether mammalian homologs behave identically was unknown
  3. 1997 High

    Cloning human p150 (PIK3R4) and showing it associates with human VPS34 to stimulate lipid kinase activity confirmed conservation of the Vps15–Vps34 mechanism in mammals and identified PI-TP as a further activator of the complex.

    Evidence cDNA cloning, recombinant protein reconstitution, lipid kinase assay, co-IP from human cell lysates

    PMID:8999962

    Open questions at the time
    • Physiological relevance of PI-TP stimulation not tested in vivo
    • Membrane recruitment mechanism in mammalian cells not defined
  4. 2002 High

    Identifying Rab5 as a GTP-dependent binding partner of p150 via its HEAT/WD40 domains, and showing p150 is required for EEA1 targeting to early endosomes, connected the VPS15–VPS34 complex to Rab GTPase-regulated endosomal identity.

    Evidence Constitutively active Rab5 overexpression, domain-deletion binding assays, fluorescence colocalization in mammalian cells

    PMID:12010460

    Open questions at the time
    • Whether Rab5 directly stimulates VPS34 kinase activity through p150 was not tested
    • Stoichiometry of Rab5–p150 interaction unknown
  5. 2003 High

    Showing that VPS34/p150 also interacts with Rab7 and that Rab7 nucleotide cycling modulates PI(3)P levels extended the regulatory framework to late endosomes, establishing that sequential Rab GTPases regulate the VPS15–VPS34 complex along the endocytic pathway.

    Evidence Co-IP, colocalization, PI3-kinase activity assays with dominant-active/negative Rab7

    PMID:14617358

    Open questions at the time
    • Direct versus indirect nature of Rab7–p150 interaction not fully resolved
    • Mechanism of Rab5-to-Rab7 handoff on the complex unclear
  6. 2006 High

    Genetic ablation of Vps15 in Drosophila proved its requirement for starvation-induced autophagy in a multicellular organism, as mutant tissues failed to form autophagosomes and accumulated ubiquitinated protein aggregates.

    Evidence Drosophila vps15 deletion mutant with GFP-Atg8a imaging, EM, and biochemical fractionation

    PMID:18326940

    Open questions at the time
    • Whether autophagy defect was solely due to loss of PI(3)P or to scaffolding functions was unclear
  7. 2009 High

    Solving the crystal structure of the yeast Vps15p WD40 domain as a seven-bladed β-propeller and mapping binding sites for Gpa1 and Atg14 revealed how Vps15 scaffolds distinct signaling and autophagy complexes through its C-terminal domain.

    Evidence X-ray crystallography with domain-deletion binding assays and genetic epistasis in yeast

    PMID:19445518

    Open questions at the time
    • Full-length Vps15 structure not solved
    • Domain rearrangements upon activation unknown
  8. 2010 High

    Systematic depletion of PI3K-III subunits showed VPS15 participates in a Beclin 1–UVRAG–BIF-1 sub-complex required for EGFR degradation and cytokinesis, expanding VPS15 function beyond autophagy to degradative endocytic trafficking and cell division.

    Evidence siRNA knockdown of each subunit with high-content microscopy in mammalian cells

    PMID:20643123

    Open questions at the time
    • How VPS15 contributes to cytokinesis mechanistically was not determined
    • Whether distinct VPS15 pools serve different sub-complexes simultaneously was unknown
  9. 2013 High

    Muscle-specific Vps15 knockout in mice caused autophagic vacuolar myopathy with lysosomal dysfunction yet preserved autophagosome formation and mTOR activity, revealing that VPS15 is essential for autophagic flux and lysosomal degradation rather than autophagosome nucleation alone.

    Evidence Conditional knockout mice, EM, immunofluorescence, Western blot, rescue by Vps15 overexpression including in Danon disease patient myoblasts

    PMID:23630012

    Open questions at the time
    • Whether residual VPS34 activity supports initial autophagosome formation in the absence of VPS15 was not dissected
    • Mechanism of mTOR escape from VPS15 loss unclear
  10. 2016 High

    Discovery that VPS15 interacts with GM130 at the cis-Golgi independently of VPS34 to regulate IFT20 sorting to the primary cilium, and that a patient R998Q mutation causes ciliopathy, revealed a novel non-canonical function of VPS15 in ciliogenesis.

    Evidence Patient fibroblast studies, zebrafish morpholino, co-IP (VPS15–GM130), humanized yeast complementation, IFT20 localization

    PMID:27882921

    Open questions at the time
    • How VPS15 recognizes GM130 structurally is unknown
    • Whether other Golgi-to-cilium cargoes are VPS15-dependent is untested
  11. 2018 High

    Mouse genetic models established that VPS15 controls neuronal migration through endosomal-lysosomal regulation of Nischarin–Pak1 signaling, and human VPS15 mutations were associated with cortical atrophy and epilepsy, linking VPS15 dysfunction to neurodevelopmental disease.

    Evidence ENU mutagenesis and conditional KO mice, live imaging, Nischarin-Pak1 pathway epistasis, human patient genotyping

    PMID:29311744

    Open questions at the time
    • Whether Nischarin accumulation is a direct consequence of impaired endosomal sorting or autophagy not fully resolved
    • Genotype-phenotype spectrum in human patients remains limited
  12. 2021 High

    Identification of VPS15 as a direct ULK kinase substrate at six phosphosites—with S861 critical for autophagosome formation and VPS34 activation—established the molecular link between autophagy initiation signaling and PI(3)P production.

    Evidence Phosphoproteomics in Ulk1/2 KO MEFs, in vitro kinase assays with phosphosite mutants, autophagy flux assays in VPS15 KO cells

    PMID:34121209

    Open questions at the time
    • Structural mechanism by which S861 phosphorylation activates VPS34 unknown
    • Whether ULK phosphorylation of VPS15 affects non-autophagic functions not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the full-length structure of VPS15 in complex with VPS34 and how conformational changes upon autophosphorylation and ULK phosphorylation activate lipid kinase activity, the identity of direct VPS15 kinase substrates, and how VPS15 partitions between VPS34-dependent and VPS34-independent (GM130–IFT20) functions at different organelles.
  • No full-length VPS15 structure or VPS15–VPS34 complex cryo-EM
  • Direct substrates of VPS15 protein kinase activity remain unidentified
  • Mechanism governing selective allocation of VPS15 to distinct sub-complexes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005768 endosome 2 GO:0005773 vacuole 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-9612973 Autophagy 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
ATG14BECN1GOLGA2PIK3C3RAB5ARAB7AULK1UVRAG
Complex memberships
PI3K-III complex I (VPS34–VPS15–Beclin 1–ATG14L)PI3K-III complex II (VPS34–VPS15–Beclin 1–UVRAG)VPS15–GM130 cis-Golgi complex

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Yeast Vps15p (PIK3R4 ortholog) is a protein kinase required for vacuolar protein sorting; kinase-inactive mutations abolish its biological activity and its ability to associate with and activate the Vps34 PI3-kinase. Short C-terminal deletions cause temperature-conditional vacuolar protein sorting defects, and unphosphorylated Vps15p is inactive, indicating autophosphorylation is required for function. Mutational analysis, in vivo phosphorylation assays, temperature-shift experiments in yeast The EMBO journal High 1756716
1993 Yeast Vps15p and Vps34p (PI3-kinase) form a membrane-associated hetero-oligomeric protein complex demonstrated by chemical cross-linking and native immunoprecipitation. Vps15p is responsible for recruiting Vps34p to intracellular membranes, and an intact Vps15p kinase domain is required for activation of Vps34p PI3-kinase activity, suggesting Vps34 lipid kinase activity is regulated by a Vps15p-mediated phosphorylation event. Chemical cross-linking, native immunoprecipitation, sucrose density gradient fractionation, kinase activity assays The EMBO journal High 8387919
1995 Vps15p (PIK3R4 ortholog) recruits Vps34p to membranes and activates its PI3-kinase activity; dominant-negative Vps34p titrates activating Vps15p, and catalytically inactive Vps15p mutants cannot associate with Vps34p, demonstrating that an intact Vps15p kinase domain is necessary for both Vps34p association and activation. Loss of Vps15p function leads to decreased cellular PtdIns(3)P levels. Dominant-negative genetics, temperature-conditional alleles, PtdIns(3)P measurement, yeast genetics The Journal of cell biology High 7721937
1997 Human p150 (PIK3R4) is a homolog of yeast Vps15p (29.6% identical, 53% similar) that associates with human VPS34 PI3-kinase in vitro in a stable manner, producing a 2-fold increase in lipid kinase activity. Addition of phosphatidylinositol transfer protein (PI-TP) further stimulates the p150·VPS34 complex 3-fold. A PI3-kinase activity co-immunoprecipitates with anti-PI-TP antisera from human cell lysates, demonstrating the in vivo interaction. cDNA cloning, recombinant protein association assay, lipid kinase activity assay, co-immunoprecipitation from cell lysates The Journal of biological chemistry High 8999962
2002 Human p150 (PIK3R4) and hVPS34 are recruited to enlarged early endosomal structures in cells expressing constitutively active Rab5, where they colocalize with EEA1. Recombinant p150 fragments disrupt endosomal EEA1 localization, showing p150 is required for EEA1 targeting. The HEAT and WD40 domains of p150 are required for GTP-dependent Rab5 binding, while deletion of the protein kinase domain increases binding to Rab5. Overexpression of constitutively active Rab5, subcellular fractionation, domain-deletion binding assays, fluorescence colocalization Traffic (Copenhagen, Denmark) High 12010460
2003 Human VPS34 and p150 (PIK3R4) are Rab7 interacting partners; the hVPS34/p150 complex colocalizes with Rab7 on late endosomes, hVPS34 PI3-kinase activity is dependent on nucleotide cycling of Rab7, and total cellular phosphatidylinositol 3-phosphate levels are modulated by Rab7 expression, linking Rab7 to regulation of hVPS34 cycling between early and late endosomes. Co-immunoprecipitation, colocalization microscopy, PI3-kinase activity assays, dominant-active/dominant-negative Rab7 expression Traffic (Copenhagen, Denmark) High 14617358
2006 Drosophila Vps15 (PIK3R4 ortholog) is required for autophagic clearance of protein aggregates; vps15 mutant fat bodies fail to accumulate GFP-Atg8a autophagic structures upon starvation, and mutant tissues accumulate ubiquitin- and Ref(2)P-positive, partially detergent-insoluble protein aggregates, providing genetic evidence for Vps15 function in autophagy in a multicellular organism. Drosophila deletion mutant, fluorescence microscopy (GFP-Atg8a), electron microscopy, biochemical fractionation, Western blotting, immunoelectron microscopy Autophagy High 18326940
2009 Yeast Vps15p WD40 domain forms a seven-bladed propeller structurally resembling G-protein beta subunits; the WD domain is sufficient to bind Gpa1 (G-protein alpha subunit) and Atg14, while the kinase and intermediate domains contribute to Gpa1 binding and are necessary for Vps15p to sustain endosomal G-protein signaling. X-ray crystallography, domain-deletion binding assays, genetic epistasis in yeast Biochemistry High 19445518
2010 A mammalian PI3K-III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 (but not ATG14L) regulates both degradative endocytic receptor trafficking and cytokinesis. siRNA depletion of individual subunits combined with high-content microscopy established that VPS15 is required for EGFR degradation and faithful cell division. siRNA-mediated depletion, high-content microscopy-based assays, localization studies Experimental cell research High 20643123
2013 Conditional knockout of Vps15 (PIK3R4) in mouse skeletal muscle causes autophagic vacuolar myopathy with accumulation of autophagosomes, glycogen, LC3, p62, and Lamp2-positive vesicles, impaired lysosomal function, and elevated creatine kinase. Contrary to expectation, Vps15-deficient cells remain competent for LC3-positive autophagosome formation and maintain mTOR activation. Ectopic overexpression of Vps15 reverts the phenotype and alleviates glycogen accumulation in Danon disease patient myoblasts. Conditional knockout mice (muscle-specific), electron microscopy, immunofluorescence, Western blotting, overexpression rescue in patient cells EMBO molecular medicine High 23630012
2016 A missense mutation in PIK3R4/VPS15 (R998Q) causes a ciliopathy phenotype. VPS15 regulates primary cilium length in human fibroblasts and ciliary processes in zebrafish. VPS15 interacts with the golgin GM130 at the Golgi and localizes there; the patient mutation impairs Golgi trafficking in humanized yeast. In patient fibroblasts carrying R998Q, IFT20 is restricted to the Golgi rather than trafficking in vesicles to the cilium, suggesting VPS15 and GM130 form a VPS34-independent complex at the cis-Golgi for IFT20-dependent sorting to the primary cilium. Patient fibroblast studies, zebrafish morpholino knockdown, co-immunoprecipitation (VPS15-GM130), humanized yeast complementation, IFT20 localization by fluorescence microscopy Nature communications High 27882921
2018 A hypomorphic mutation in Vps15 (PIK3R4) in mice perturbs endosomal-lysosomal trafficking and autophagy, resulting in upregulation of Nischarin which inhibits Pak1 signaling, causing defective neuronal migration and a fractured hippocampal pyramidal cell layer. Complete ablation of Vps15 causes accumulation of autophagic substrates, apoptosis induction, and severe cortical atrophy. Mutations in human VPS15 are associated with cortical atrophy and epilepsy. ENU mutagenesis mouse model, conditional knockout, live imaging, Western blotting, pathway epistasis (Nischarin-Pak1), human patient genotyping Nature neuroscience High 29311744
2021 ULK kinase phosphorylates VPS15 (PIK3R4) at six sites; mutation of these phosphorylation sites reduces autophagosome formation and decreases VPS34 lipid kinase activity in vitro. Serine 861, the major VPS15 phosphosite, is specifically required for both autophagy initiation and autophagic flux. VPS15 knockout cells reveal ULK-dependent phenotypes that can be partially recapitulated by chronic VPS34 inhibition, positioning VPS15 as a substrate linking ULK and VPS34 in autophagy regulation. Unbiased phosphoproteomics in Ulk1/2 KO MEFs, in vitro VPS34 kinase assay with phosphosite mutants, autophagy flux assays in VPS15 KO cells The EMBO journal High 34121209
1999 Pichia pastoris Vps15 homolog (PpVPS15, PIK3R4 ortholog) is required for selective peroxisome autophagy; deletion of PpVPS15 prevents vacuolar uptake of peroxisomes upon glucose or ethanol addition, indicating Vps15 function is required at an early stage in peroxisome degradation. Gene deletion in yeast, enzyme activity assays, electron microscopy Current genetics Medium 10591966

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1987 Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annual review of medicine 1077 3555290
1983 A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. The Journal of experimental medicine 1018 6196430
2009 Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning. The Journal of cell biology 560 19564404
1984 Inherited deficiency of the Mac-1, LFA-1, p150,95 glycoprotein family and its molecular basis. The Journal of experimental medicine 475 6096477
1987 Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface. The Journal of clinical investigation 443 3038962
2004 Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology 348 15326253
1987 Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency. Cell 348 3594570
1995 The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication. Cell 327 7600578
1993 A membrane-associated complex containing the Vps15 protein kinase and the Vps34 PI 3-kinase is essential for protein sorting to the yeast lysosome-like vacuole. The EMBO journal 300 8387919
1986 Regulated expression of the Mac-1, LFA-1, p150,95 glycoprotein family during leukocyte differentiation. Journal of immunology (Baltimore, Md. : 1950) 295 2428876
1987 cDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein, p150,95. The EMBO journal 263 3327687
1989 Adherence of neutrophils to cultured human microvascular endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1, LFA-1, p150,95 glycoprotein family. The Journal of clinical investigation 250 2521491
1988 Neutrophil and monocyte cell surface p150,95 has iC3b-receptor (CR4) activity resembling CR3. The Journal of clinical investigation 247 2969921
1987 Role of the adherence-promoting receptors, CR3, LFA-1, and p150,95, in binding of Histoplasma capsulatum by human macrophages. The Journal of experimental medicine 216 3025331
1987 The primary structure of the beta-subunit of the cell surface adhesion glycoproteins LFA-1, CR3 and p150,95 and its relationship to the fibronectin receptor. The EMBO journal 205 2954816
1995 Vesicle-mediated protein transport: regulatory interactions between the Vps15 protein kinase and the Vps34 PtdIns 3-kinase essential for protein sorting to the vacuole in yeast. The Journal of cell biology 204 7721937
2002 A role for regulated binding of p150(Glued) to microtubule plus ends in organelle transport. The Journal of cell biology 197 12119357
1985 p150/95, Third member of the LFA-1/CR3 polypeptide family identified by anti-Leu M5 monoclonal antibody. European journal of immunology 196 3924634
1985 Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95. European journal of immunology 193 2933266
1997 Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex. The Journal of biological chemistry 191 8999962
1992 The Mac-1 and p150,95 beta 2 integrins bind denatured proteins to mediate leukocyte cell-substrate adhesion. Experimental cell research 180 1572393
1988 Relative contribution of the leukocyte molecules Mo1, LFA-1, and p150,95 (LeuM5) in adhesion of granulocytes and monocytes to vascular endothelium is tissue- and stimulus-specific. Journal of cellular physiology 177 3056960
2002 Evidence that an interaction between EB1 and p150(Glued) is required for the formation and maintenance of a radial microtubule array anchored at the centrosome. Molecular biology of the cell 161 12388762
1989 High affinity binding protein for the regulatory subunit of cAMP-dependent protein kinase II-B. Cloning, characterization, and expression of cDNAs for rat brain P150. The Journal of biological chemistry 161 2538452
2002 Role of Rab5 in the recruitment of hVps34/p150 to the early endosome. Traffic (Copenhagen, Denmark) 160 12010460
1986 The p150,95 molecule is a marker of human mononuclear phagocytes: comparison with expression of class II molecules. European journal of immunology 160 3456894
2010 A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic. Experimental cell research 154 20643123
1987 Role of p150,95 in adhesion, migration, chemotaxis and phagocytosis of human monocytes. European journal of immunology 153 2958296
2003 Human VPS34 and p150 are Rab7 interacting partners. Traffic (Copenhagen, Denmark) 140 14617358
1986 p150,95, the third member of the Mac-1, LFA-1 human leukocyte adhesion glycoprotein family. Journal of immunology (Baltimore, Md. : 1950) 133 3510003
1991 Leukocyte integrin P150,95 (CD11c/CD18) functions as an adhesion molecule binding to a counter-receptor on stimulated endothelium. Journal of immunology (Baltimore, Md. : 1950) 132 1702811
1997 Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin-related motor HsEg5 to the dynactin subunit p150. The Journal of biological chemistry 124 9235942
2008 The HP1-p150/CAF-1 interaction is required for pericentric heterochromatin replication and S-phase progression in mouse cells. Nature structural & molecular biology 122 19172751
1990 Lipophosphoglycan from Leishmania mexicana promastigotes binds to members of the CR3, p150,95 and LFA-1 family of leukocyte integrins. Journal of immunology (Baltimore, Md. : 1950) 120 1972169
1994 The leukocyte integrin p150,95 (CD11c/CD18) as a receptor for iC3b. Activation by a heterologous beta subunit and localization of a ligand recognition site to the I domain. Journal of immunology (Baltimore, Md. : 1950) 116 7512600
2012 The p150(Glued) CAP-Gly domain regulates initiation of retrograde transport at synaptic termini. Neuron 110 22542187
2009 The retromer component SNX6 interacts with dynactin p150(Glued) and mediates endosome-to-TGN transport. Cell research 101 19935774
1985 Isolation of complement-fragment-iC3b-binding proteins by affinity chromatography. The identification of p150,95 as an iC3b-binding protein. The Biochemical journal 99 4062888
1991 A genetic and structural analysis of the yeast Vps15 protein kinase: evidence for a direct role of Vps15p in vacuolar protein delivery. The EMBO journal 96 1756716
1987 Membrane glycoprotein p150,95 of human cytotoxic T cell clone is involved in conjugate formation with target cells. Journal of immunology (Baltimore, Md. : 1950) 96 3106475
1988 Chromosomal location of the genes encoding the leukocyte adhesion receptors LFA-1, Mac-1 and p150,95. Identification of a gene cluster involved in cell adhesion. The Journal of experimental medicine 94 3284962
2013 Defects of Vps15 in skeletal muscles lead to autophagic vacuolar myopathy and lysosomal disease. EMBO molecular medicine 93 23630012
2006 Microtubule plus-end loading of p150(Glued) is mediated by EB1 and CLIP-170 but is not required for intracellular membrane traffic in mammalian cells. Journal of cell science 90 16772339
2007 The G59S mutation in p150(glued) causes dysfunction of dynactin in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 89 18094236
1985 Deficiency of the adhesive protein complex lymphocyte function antigen 1, complement receptor type 3, glycoprotein p150,95 in a girl with recurrent bacterial infections. Effects on phagocytic cells and lymphocyte functions. The Journal of clinical investigation 88 2934411
2008 Huntingtin regulates RE1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) nuclear trafficking indirectly through a complex with REST/NRSF-interacting LIM domain protein (RILP) and dynactin p150 Glued. The Journal of biological chemistry 87 18922795
1986 Ligand binding by the p150,95 antigen of U937 monocytic cells: properties in common with complement receptor type 3 (CR3). European journal of immunology 87 3530784
2021 Decoupling expression and editing preferences of ADAR1 p150 and p110 isoforms. Proceedings of the National Academy of Sciences of the United States of America 84 33723056
2003 The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1. Molecular and cellular biology 78 12697822
2000 The p150-Spir protein provides a link between c-Jun N-terminal kinase function and actin reorganization. Current biology : CB 78 10744979
2013 Dynactin subunit p150(Glued) is a neuron-specific anti-catastrophe factor. PLoS biology 73 23874158
2004 p150 overexpression in gastric carcinoma: the association with p53, apoptosis and cell proliferation. International journal of cancer 70 15382063
1998 Expression of p150 in cervical neoplasia and its potential value in predicting survival. Cancer 68 9762939
2004 p150(Sal2) is a p53-independent regulator of p21(WAF1/CIP). Molecular and cellular biology 67 15082782
2000 Comparative studies of the colonic in situ expression of intercellular adhesion molecules (ICAM-1, -2, and -3), beta2 integrins (LFA-1, Mac-1, and p150,95), and PECAM-1 in ulcerative colitis and Crohn's disease. The American journal of surgical pathology 63 10935652
1990 Genomic structure of an integrin alpha subunit, the leukocyte p150,95 molecule. The Journal of biological chemistry 62 2303426
1988 Modulation of surface CD11/CD18 glycoproteins (Mo1, LFA-1, p150,95) by human mononuclear phagocytes. Clinical immunology and immunopathology 62 3123109
1986 The genetic deficiency of leukocyte surface glycoprotein Mac-1, LFA-1, p150,95 in humans is associated with defective antibody-dependent cellular cytotoxicity in vitro and defective protection against herpes simplex virus infection in vivo. Journal of immunology (Baltimore, Md. : 1950) 61 3528287
2008 The PI 3-kinase regulator Vps15 is required for autophagic clearance of protein aggregates. Autophagy 60 18326940
2006 The replication kinase Cdc7-Dbf4 promotes the interaction of the p150 subunit of chromatin assembly factor 1 with proliferating cell nuclear antigen. EMBO reports 58 16826239
1999 Intracellular distribution of rubella virus nonstructural protein P150. Journal of virology 57 10438871
1988 Co-expression of Mac-1 and p150,95 on CD5+ B cells. Structural and functional characterization in a human chronic lymphocytic leukemia. European journal of immunology 56 2456938
2014 Nuclear translocation of IGF-1R via p150(Glued) and an importin-β/RanBP2-dependent pathway in cancer cells. Oncogene 55 24909165
2016 A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi. Nature communications 53 27882921
2021 Phosphoproteomic identification of ULK substrates reveals VPS15-dependent ULK/VPS34 interplay in the regulation of autophagy. The EMBO journal 51 34121209
1985 Leukocyte LFA-1, OKM1, p150,95 deficiency syndrome: functional and biosynthetic studies of three kindreds. Federation proceedings 50 3891420
2010 Par6 alpha interacts with the dynactin subunit p150 Glued and is a critical regulator of centrosomal protein recruitment. Molecular biology of the cell 48 20719959
2019 IL6R-STAT3-ADAR1 (P150) interplay promotes oncogenicity in multiple myeloma with 1q21 amplification. Haematologica 46 31413087
1993 Characterization of the p150,95 leukocyte integrin alpha subunit (CD11c) gene promoter. Identification of cis-acting elements. The Journal of biological chemistry 46 7678251
1989 Increased expression of p150,95 and CR3 leukocyte adhesion molecules by mononuclear phagocytes in rheumatoid synovial membranes. Comparison with osteoarthritic and normal synovial membranes. Arthritis and rheumatism 45 2569874
1994 Regulated expression of p150,95 (CD11c/CD18; alpha X/beta 2) and VLA-4 (CD49d/CD29; alpha 4/beta 1) integrins during myeloid cell differentiation. European journal of immunology 41 8020569
2001 A truncated form of the human CAF-1 p150 subunit impairs the maintenance of transcriptional gene silencing in mammalian cells. Molecular and cellular biology 40 11238931
2018 Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans. Nature neuroscience 39 29311744
2007 p150/95 (CD11c/CD18) expression is required for the development of experimental autoimmune encephalomyelitis. The American journal of pathology 39 17525267
2010 Overexpression of p150, a part of the large subunit of the eukaryotic translation initiation factor 3, in colon cancer. Anticancer research 38 20530408
2001 Characterization of four CD18 mutants in leucocyte adhesion deficient (LAD) patients with differential capacities to support expression and function of the CD11/CD18 integrins LFA-1, Mac-1 and p150,95. Clinical and experimental immunology 38 11703376
2003 Complementation of a deletion in the rubella virus p150 nonstructural protein by the viral capsid protein. Journal of virology 37 12915564
2020 The p150 Isoform of ADAR1 Blocks Sustained RLR signaling and Apoptosis during Influenza Virus Infection. PLoS pathogens 36 32898178
2011 Interaction of mammalian end binding proteins with CAP-Gly domains of CLIP-170 and p150(glued). Journal of structural biology 36 22119847
1999 A Pichia pastoris VPS15 homologue is required in selective peroxisome autophagy. Current genetics 36 10591966
1987 Biosynthesis and glycosylation of p150,95 and related leukocyte adhesion proteins. Journal of immunology (Baltimore, Md. : 1950) 36 3298434
2014 A separable domain of the p150 subunit of human chromatin assembly factor-1 promotes protein and chromosome associations with nucleoli. Molecular biology of the cell 35 25057015
2012 TRAPPC9 mediates the interaction between p150 and COPII vesicles at the target membrane. PloS one 35 22279557
2004 The p150-Glued Ssm4p regulates microtubular dynamics and nuclear movement in fission yeast. Journal of cell science 35 15509865
2014 Structural basis for the extended CAP-Gly domains of p150(glued) binding to microtubules and the implication for tubulin dynamics. Proceedings of the National Academy of Sciences of the United States of America 34 25059720
2006 ird1 is a Vps15 homologue important for antibacterial immune responses in Drosophila. Cellular microbiology 34 17166233
2012 The dynactin p150 subunit: cell biology studies of sequence changes found in ALS/MND and Parkinsonian syndromes. Journal of neural transmission (Vienna, Austria : 1996) 33 23143281
1995 Identification of Sp1-binding sites in the CD11c (p150,95 alpha) and CD11a (LFA-1 alpha) integrin subunit promoters and their involvement in the tissue-specific expression of CD11c. European journal of immunology 33 8566043
2001 A tumor host range selection procedure identifies p150(sal2) as a target of polyoma virus large T antigen. Proceedings of the National Academy of Sciences of the United States of America 32 11734654
1986 Binding of the adhesive protein complex (LFA-1/Mac-1/p150,95) to concanavalin A. Journal of leukocyte biology 31 3510266
1999 M phase phosphorylation of cytoplasmic dynein intermediate chain and p150(Glued). The Journal of biological chemistry 30 10318847
2010 Aurora A contributes to p150(glued) phosphorylation and function during mitosis. The Journal of cell biology 29 20479466
2009 Structure and function of Vps15 in the endosomal G protein signaling pathway. Biochemistry 29 19445518
2004 p150(Glued), Dynein, and microtubules are specifically required for activation of MKK3/6 and p38 MAPKs. The Journal of biological chemistry 29 15375157
2018 Genetic ablation of dynactin p150Glued in postnatal neurons causes preferential degeneration of spinal motor neurons in aged mice. Molecular neurodegeneration 28 29490687
2011 In vivo roles of the basic domain of dynactin p150 in microtubule plus-end tracking and dynein function. Traffic (Copenhagen, Denmark) 27 22106867
1996 The beta 2 integrin Mac-1 but not p150,95 associates with Fc gamma RIIA. European journal of immunology 27 8566068
1995 Heterogenous glycosylation of ICAM-3 and lack of interaction with Mac-1 and p150,95. European journal of immunology 27 7737271
2018 Interactions between monomeric CCTδ and p150Glued: A novel function for CCTδ at the cell periphery distinct from the protein folding activity of the molecular chaperone CCT. Experimental cell research 26 29913154
2018 Retrograde Degenerative Signaling Mediated by the p75 Neurotrophin Receptor Requires p150Glued Deacetylation by Axonal HDAC1. Developmental cell 26 30086304