PIK3C3

Summary

Gene Symbol: PIK3C3
Description: phosphatidylinositol 3-kinase catalytic subunit type 3
Alias: VPS34, Vps34, hVps34, phosphatidylinositol 3-kinase catalytic subunit type 3, PI3-kinase type 3, PI3K type 3, PtdIns-3-kinase type 3, phosphatidylinositol 3-kinase p100 subunit, phosphoinositide-3-kinase, class 3
Species: human
Products:     PIK3C3

Top Publications

  1. He S, Ni D, Ma B, Lee J, Zhang T, Ghozalli I, et al. PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex. Nat Cell Biol. 2013;15:1206-1219 pubmed publisher
  2. Volinia S, Dhand R, Vanhaesebroeck B, MacDougall L, Stein R, Zvelebil M, et al. A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. EMBO J. 1995;14:3339-48 pubmed
    ..These results suggest that the major components of the yeast Vps intracellular trafficking complex are conserved in humans. ..
  3. Deregibus M, Cantaluppi V, Doublier S, Brizzi M, Deambrosis I, Albini A, et al. HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells. J Biol Chem. 2002;277:25195-202 pubmed
  4. Vergne I, Chua J, Deretic V. Tuberculosis toxin blocking phagosome maturation inhibits a novel Ca2+/calmodulin-PI3K hVPS34 cascade. J Exp Med. 2003;198:653-9 pubmed
    ..Ca2+ and calmodulin were required for a newly uncovered Ca2+/calmodulin phosphatidylinositol (PI)3 kinase hVPS34 cascade, essential for production of PI 3 phosphate (PI3P) on liposomes in vitro and on phagosomes in vivo...
  5. Stein M, Feng Y, Cooper K, Welford A, Wandinger Ness A. Human VPS34 and p150 are Rab7 interacting partners. Traffic. 2003;4:754-71 pubmed
    ..Rab7 is required for late endosomal transport and here we establish that the phosphatidylinositol 3'-kinase hVPS34 and its adaptor protein p150 are rab7 interacting partners...
  6. Stopkova P, Saito T, Papolos D, Vevera J, Paclt I, Zukov I, et al. Identification of PIK3C3 promoter variant associated with bipolar disorder and schizophrenia. Biol Psychiatry. 2004;55:981-8 pubmed
    ..One is PIK3C3, a member of the phosphatidylinositide 3-kinase family that maps closely to markers on 18q linked to both BD and ..
  7. Byfield M, Murray J, Backer J. hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J Biol Chem. 2005;280:33076-82 pubmed
    ..We now present evidence that the Class III PI 3-kinase, hVps34, also regulates S6K1, and is a critical component of the nutrient sensing apparatus...
  8. Nobukuni T, Joaquin M, Roccio M, Dann S, Kim S, Gulati P, et al. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci U S A. 2005;102:14238-43 pubmed
    ..amino acids control mTOR signaling is distinct from that of insulin and that, instead of signaling through components of the insulin/class 1 PI3K pathway, amino acids mediate mTOR activation by signaling through class 3 PI3K, hVps34.
  9. Pattingre S, Tassa A, Qu X, Garuti R, Liang X, Mizushima N, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122:927-39 pubmed
    ..This antiautophagy function of Bcl-2 may help maintain autophagy at levels that are compatible with cell survival, rather than cell death. ..

More Information

Publications104 found, 100 shown here

  1. Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q. Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. Proc Natl Acad Sci U S A. 2008;105:19211-6 pubmed publisher
  2. Chen X, Cheng L, Jia X, Zeng Y, Yao S, Lv Z, et al. Human immunodeficiency virus type 1 Tat accelerates Kaposi sarcoma-associated herpesvirus Kaposin A-mediated tumorigenesis of transformed fibroblasts in vitro as well as in nude and immunocompetent mice. Neoplasia. 2009;11:1272-84 pubmed
  3. Di Bartolomeo S, Corazzari M, Nazio F, Oliverio S, Lisi G, Antonioli M, et al. The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. J Cell Biol. 2010;191:155-68 pubmed publisher
    ..Autophagy initiation signaling requires both the ULK1 kinase and the BECLIN 1-VPS34 core complex to generate autophagosomes, double-membraned vesicles that transfer cellular contents to lysosomes...
  4. Panaretou C, Domin J, Cockcroft S, Waterfield M. 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. J Biol Chem. 1997;272:2477-85 pubmed
    Genetic and biochemical studies have shown that the phosphatidylinositol (PtdIns) 3-kinase encoded by the yeast VPS34 gene is required for the efficient sorting and delivery of proteins to the vacuole...
  5. Fimia G, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R, et al. Ambra1 regulates autophagy and development of the nervous system. Nature. 2007;447:1121-5 pubmed
  6. Tang R, Zhao X, Fang C, Tang W, Huang K, Wang L, et al. Investigation of variants in the promoter region of PIK3C3 in schizophrenia. Neurosci Lett. 2008;437:42-4 pubmed publisher
    The PIK3C3 gene has been implicated as a candidate gene for schizophrenia by functional evidence and genetic association studies. A series of previous studies have found susceptibility SNPs in promoter region...
  7. Itakura E, Kishi C, Inoue K, Mizushima N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol Biol Cell. 2008;19:5360-72 pubmed publisher
    ..In yeast, two distinct PI3-kinase complexes are known: complex I (Vps34, Vps15, Vps30/Atg6, and Atg14) is involved in autophagy, and complex II (Vps34, Vps15, Vps30/Atg6, and Vps38) ..
  8. Yan Y, Flinn R, Wu H, Schnur R, Backer J. hVps15, but not Ca2+/CaM, is required for the activity and regulation of hVps34 in mammalian cells. Biochem J. 2009;417:747-55 pubmed publisher
    The mammalian Class III PI3K (phosphoinositide 3-kinase), hVps34 [mammalian Vps (vacuolar protein sorting) 34 homologue], is an important regulator of vesicular trafficking, autophagy and nutrient sensing...
  9. Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, et al. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol. 2009;11:385-96 pubmed publisher
    Beclin 1, a protein essential for autophagy, binds to hVps34/Class III phosphatidylinositol-3-kinase and UVRAG. Here, we have identified two Beclin 1 associated proteins, Atg14L and Rubicon...
  10. Sagona A, Nezis I, Pedersen N, Liestøl K, Poulton J, Rusten T, et al. PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody. Nat Cell Biol. 2010;12:362-71 pubmed publisher
    ..Depletion of the VPS34 or Beclin 1 subunits of PI(3)K-III causes cytokinesis arrest and an increased number of binucleate and ..
  11. Thoresen S, Pedersen N, Liestøl K, Stenmark H. A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic. Exp Cell Res. 2010;316:3368-78 pubmed publisher
    ..with siRNA-mediated depletion of individual subunits indicated that a specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates both receptor degradation and cytokinesis, whereas ATG14L, a PI3K-III subunit ..
  12. Sun Q, Zhang J, Fan W, Wong K, Ding X, Chen S, et al. The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression. J Biol Chem. 2011;286:185-91 pubmed publisher
    ..Here, we demonstrate that Rubicon interacts with the PI3KC3 catalytic subunit hVps34 via its RUN domain...
  13. Bodemann B, Orvedahl A, Cheng T, Ram R, Ou Y, Formstecher E, et al. RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly. Cell. 2011;144:253-67 pubmed publisher
    ..Through direct binding to Exo84, RalB induces the assembly of catalytically active ULK1 and Beclin1-VPS34 complexes on the exocyst, which are required for isolation membrane formation and maturation...
  14. Kim J, Kim Y, Fang C, Russell R, Kim J, Fan W, et al. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell. 2013;152:290-303 pubmed publisher
    ..The class III phosphatidylinositol-3 kinase, Vps34, forms multiple complexes and regulates both intracellular vesicle trafficking and autophagy induction...
  15. Xia P, Wang S, Du Y, Zhao Z, Shi L, Sun L, et al. WASH inhibits autophagy through suppression of Beclin 1 ubiquitination. EMBO J. 2013;32:2685-96 pubmed publisher
    ..The lysine 437 ubiquitination of Beclin 1 enhances the association with Vps34 to promote Vps34 activity...
  16. Furuya N, Yu J, Byfield M, Pattingre S, Levine B. The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy. 2005;1:46-52 pubmed
    ..function as a VPS and autophagy protein as part of a complex with Class III phosphatidylinositol 3'-kinase (PI3K)/Vps34. However, nothing is known about which domains of Atg6/Beclin 1 are required for its functional activity and ..
  17. Du X, Liu G, Loor J, Fang Z, Bucktrout R, Yang Y, et al. Impaired hepatic autophagic activity in dairy cows with severe fatty liver is associated with inflammation and reduced liver function. J Dairy Sci. 2018;101:11175-11185 pubmed publisher
    ..autophagosome formation-related genes, beclin 1 (BECN1), phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), autophagy-related gene (ATG) 3, ATG5, and ATG12, did not differ...
  18. Wang Q, Guo W, Hao B, Shi X, Lu Y, Wong C, et al. Mechanistic study of TRPM2-Ca(2+)-CAMK2-BECN1 signaling in oxidative stress-induced autophagy inhibition. Autophagy. 2016;12:1340-54 pubmed publisher
    ..Ser295 phosphorylation of BECN1 in turn decreased the association between BECN1 and PIK3C3/VPS34, but induced binding between BECN1 and BCL2...
  19. Stein K, Chiang H. Exocytosis and Endocytosis of Small Vesicles across the Plasma Membrane in Saccharomyces cerevisiae. Membranes (Basel). 2014;4:608-29 pubmed publisher
    ..FBPase internalization also requires the VPS34 gene encoding PI3K...
  20. Larrue C, Saland E, Boutzen H, Vergez F, David M, Joffre C, et al. Proteasome inhibitors induce FLT3-ITD degradation through autophagy in AML cells. Blood. 2016;127:882-92 pubmed publisher
    ..Using pharmacologic inhibitors of autophagy, specific downregulation of key autophagy proteins including Vps34, autophagy gene (Atg)5, Atg12, Atg13, biochemical, and microscopy studies, we demonstrated that proteasome ..
  21. Wu F, Fang T, Yu L, Lv G, Lv H, Liang D, et al. ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1?. J Hepatol. 2016;65:314-24 pubmed publisher
    ..Notably, ADRB2 signaling negatively regulated autophagy by disrupting Beclin1/VPS34/Atg14 complex in an Akt-dependent manner, leading to HIF1? stabilization, reprogramming of HCC cells glucose ..
  22. Lu Q, Yao Y, Hu Z, Hu C, Song Q, Ye J, et al. Angiogenic Factor AGGF1 Activates Autophagy with an Essential Role in Therapeutic Angiogenesis for Heart Disease. PLoS Biol. 2016;14:e1002529 pubmed publisher
    ..Mechanistically, AGGF1 initiates autophagy by activating JNK, which leads to activation of Vps34 lipid kinase and the assembly of Becn1-Vps34-Atg14 complex involved in the initiation of autophagy...
  23. Seca H, Lima R, Lopes Rodrigues V, Guimarães J, Almeida G, Vasconcelos M. Targeting miR-21 induces autophagy and chemosensitivity of leukemia cells. Curr Drug Targets. 2013;14:1135-43 pubmed
    ..Treatment with antimiR-21 caused an increase in the autophagy related proteins Beclin-1, Vps34 and LC3-II...
  24. Gulbins A, Schumacher F, Becker K, Wilker B, Soddemann M, Boldrin F, et al. Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide. Mol Psychiatry. 2018;23:2324-2346 pubmed publisher
    ..ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B...
  25. Corona Velazquez A, Jackson W. So Many Roads: the Multifaceted Regulation of Autophagy Induction. Mol Cell Biol. 2018;38: pubmed publisher
    ..We discuss reports of MTOR-independent, AMPK-independent, ULK1/2-independent, and BECN1-PIK3C3-independent autophagy...
  26. Huang R, Quan Y, Chen J, Wang T, Xu M, Ye M, et al. Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway. Cell Physiol Biochem. 2017;41:1851-1864 pubmed publisher
    ..Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared by RT-PCR and Western blot...
  27. Cinque L, Forrester A, Bartolomeo R, Svelto M, Venditti R, Montefusco S, et al. FGF signalling regulates bone growth through autophagy. Nature. 2015;528:272-5 pubmed publisher
    ..mediated by the growth factor FGF18 through FGFR4 and JNK-dependent activation of the autophagy initiation complex VPS34-beclin-1...
  28. Toton E, Lisiak N, Sawicka P, Rybczynska M. Beclin-1 and its role as a target for anticancer therapy. J Physiol Pharmacol. 2014;65:459-67 pubmed
    ..Atg14L, UVRAG, Bif-1, Rubicon, Ambra1, HMGB1, IP3R, PINK and survivin) to promote the formation of the Beclin-1-Vps34-Vps15 complex which triggers the autophagy protein cascade...
  29. Yoshida S, Anraku Y. Characterization of staurosporine-sensitive mutants of Saccharomyces cerevisiae: vacuolar functions affect staurosporine sensitivity. Mol Gen Genet. 2000;263:877-88 pubmed
    ..integration mapping showed that the genes STT2/ STT6, STT5, STT7, STT8 and STT9 are allelic to VPS18, ERG10, GPI1, VPS34 and VPS11, respectively...
  30. Mohan N, Shen Y, Dokmanovic M, Endo Y, Hirsch D, Wu W. VPS34 regulates TSC1/TSC2 heterodimer to mediate RheB and mTORC1/S6K1 activation and cellular transformation. Oncotarget. 2016;7:52239-52254 pubmed publisher
    b>VPS34 is reported to activate S6K1 and is implicated in regulating cell growth, the mechanisms of which remain elusive...
  31. Chen R, Wang H, Liang B, Liu G, Tang M, Jia R, et al. Downregulation of ASPP2 improves hepatocellular carcinoma cells survival via promoting BECN1-dependent autophagy initiation. Cell Death Dis. 2016;7:e2512 pubmed publisher
    ..through regulating BECN1 transcription and formation of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) complex...
  32. Law F, Seo J, Wang Z, Deleon J, Bolis Y, Brown A, et al. The VPS34 PI3K negatively regulates RAB-5 during endosome maturation. J Cell Sci. 2017;130:2007-2017 pubmed publisher
    ..Rab5 isoforms, Rab5a and Rab5b) is increased in Vps34-knockout mouse embryonic fibroblasts (Vps34 is also known as PIK3C3 in mammals)...
  33. Kim Y, Chang S, Kwon J, Rhee S. HIV-1 Nef plays an essential role in two independent processes in CD4 down-regulation: dissociation of the CD4-p56(lck) complex and targeting of CD4 to lysosomes. Virology. 1999;257:208-19 pubmed
  34. Rao A, Freishtat R, Jalagadugula G, Singh A, Mao G, Wiles A, et al. Alterations in insulin-signaling and coagulation pathways in platelets during hyperglycemia-hyperinsulinemia in healthy non-diabetic subject. Thromb Res. 2014;134:704-10 pubmed publisher
    ..Monocyte, PIK3C3, PTPN11 and TFPI were downregulated...
  35. Compton L, Ikonomov O, Sbrissa D, Garg P, Shisheva A. 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. Am J Physiol Cell Physiol. 2016;311:C366-77 pubmed publisher
    The two evolutionarily conserved mammalian lipid kinases Vps34 and PIKfyve are involved in an important physiological relationship, whereby the former produces phosphatidylinositol (PtdIns) 3P that is used as a substrate for PtdIns(3,5)..
  36. Yuan H, Russell R, Guan K. Regulation of PIK3C3/VPS34 complexes by MTOR in nutrient stress-induced autophagy. Autophagy. 2013;9:1983-95 pubmed
    ..The type III phosphatidylinositol (PtdIns) 3-kinase, whose catalytic subunit is PIK3C3/VPS34, plays a critical role in intracellular membrane trafficking and autophagy induction...
  37. Young C, Arteaga C, Cook R. Dual inhibition of Type I and Type III PI3 kinases increases tumor cell apoptosis in HER2+ breast cancers. Breast Cancer Res. 2015;17:148 pubmed publisher
    ..Sequence analysis of EZN4150 revealed significant homology to the gene encoding the type III PI3K, Vps34, a key component for autophagy induction. EZN4150 simultaneously reduced expression of both p110α and Vps34...
  38. He F, Agosto M, Anastassov I, Tse D, Wu S, Wensel T. Phosphatidylinositol-3-phosphate is light-regulated and essential for survival in retinal rods. Sci Rep. 2016;6:26978 pubmed publisher
    ..This increase was blocked in a rod-specific knockout of the PI-3 kinase Vps34, resulting in failure of endosomal and autophagy-related membranes to fuse with lysosomes, and accumulation of ..
  39. Liu J, Wu P, Wang Y, Du Y, A N, Liu S, et al. Ad-HGF improves the cardiac remodeling of rat following myocardial infarction by upregulating autophagy and necroptosis and inhibiting apoptosis. Am J Transl Res. 2016;8:4605-4627 pubmed
    ..In addition, Ad-HGF markedly increased the formation of Beclin1-Vps34-Atg14L complex, which accounted for promoting autophagy...
  40. Naufer A, Hipolito V, Ganesan S, Prashar A, Zaremberg V, Botelho R, et al. pH of endophagosomes controls association of their membranes with Vps34 and PtdIns(3)P levels. J Cell Biol. 2018;217:329-346 pubmed publisher
    ..We found that this is the product of a pH-based mechanism that induces the dissociation of the Vps34 class III phosphatidylinositol-3-kinase from these organelles as they acidify...
  41. Kariuki S, Franek B, Mikolaitis R, Utset T, Jolly M, Skol A, et al. Promoter variant of PIK3C3 is associated with autoimmunity against Ro and Sm epitopes in African-American lupus patients. J Biomed Biotechnol. 2010;2010:826434 pubmed publisher
    The PIK3C3 locus was implicated in case-case genome-wide association study of systemic lupus erythematosus (SLE) which we had performed to detect genes associated with autoantibodies and serum interferon-alpha (IFN-alpha)...
  42. Zhang H, Sang W, Ruan Z, Wang Y. Akt/Nox2/NF-?B signaling pathway is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation. Arch Biochem Biophys. 2011;505:266-72 pubmed publisher
  43. Tanigawa M, Maeda T. An In Vitro TORC1 Kinase Assay That Recapitulates the Gtr-Independent Glutamine-Responsive TORC1 Activation Mechanism on Yeast Vacuoles. Mol Cell Biol. 2017;37: pubmed publisher
    ..specifically responds to l-glutamine, resides on the vacuolar membranes, and involves a previously uncharacterized Vps34-Vps15 phosphatidylinositol (PI) 3-kinase complex and the PI-3-phosphate [PI(3)P]-binding FYVE domain-containing ..
  44. Schnatwinkel C, Christoforidis S, Lindsay M, Uttenweiler Joseph S, Wilm M, Parton R, et al. The Rab5 effector Rabankyrin-5 regulates and coordinates different endocytic mechanisms. PLoS Biol. 2004;2:E261 pubmed
    ..Furthermore, its active role in apical pinocytosis in epithelial cells suggests an important function of Rabankyrin-5 in the physiology of polarised cells. ..
  45. Yang Y, Fiskus W, Yong B, Atadja P, Takahashi Y, Pandita T, et al. Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy. Proc Natl Acad Sci U S A. 2013;110:6841-6 pubmed publisher
    ..However, how autophagy-inducing stress regulates Vps34 activity has not been fully elucidated...
  46. Blagoveshchenskaya A, Thomas L, Feliciangeli S, Hung C, Thomas G. HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway. Cell. 2002;111:853-66 pubmed
    ..These data provide new insights into the cellular basis of HIV-1 immunoevasion. ..
  47. Hegedűs K, Takáts S, Boda A, Jipa A, Nagy P, Varga K, et al. The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy. Mol Biol Cell. 2016;27:3132-3142 pubmed
    ..recruitment of Rab7 to PI3P-positive autophagosomes, which are generated by the action of the Atg14-containing Vps34 PI3 kinase complex. Finally, we find that Rab5 is required for proper lysosomal function...
  48. Fogel A, Dlouhy B, Wang C, Ryu S, Neutzner A, Hasson S, et al. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy. Mol Cell Biol. 2013;33:3675-88 pubmed publisher
    ..We map these novel phosphorylation sites to serines 90 and 93 and demonstrate that phosphorylation at these sites is necessary for maximal autophagy. These results help clarify the mechanism of beclin-1 and Atg14 during autophagy. ..
  49. Wei Y, An Z, Zou Z, Sumpter R, Su M, Zang X, et al. The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation. elife. 2015;4: pubmed publisher
  50. Rutledge R, Ghislain M, Mullins J, de Thozée C, Golin J. Pdr5-mediated multidrug resistance requires the CPY-vacuolar sorting protein Vps3: are xenobiotic compounds routed from the vacuole to plasma membrane transporters for efflux?. Mol Genet Genomics. 2008;279:573-83 pubmed publisher
    ..A similar phenotype is also observed with deletions of VPS15, VPS34, and VPS38, which encode essential members of the carboxypeptidase Y vacuolar protein-sorting pathway...
  51. Yu X, Long Y, Shen H. Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy. Autophagy. 2015;11:1711-28 pubmed publisher
    ..In contrast, the class III PtdIns3K catalytic subunit PIK3C3/Vps34 forms a protein complex with BECN1 and PIK3R4 and produces phosphatidylinositol 3-phosphate (PtdIns3P), ..
  52. Lee C, Liu Q, Tomkowicz B, Yi Y, Freedman B, Collman R. Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways. J Leukoc Biol. 2003;74:676-82 pubmed
    ..Targeting these cellular signaling pathways may have benefit in controlling inflammatory sequelae of HIV infection such as in neurological disease. ..
  53. Huang J, Yang J, Shen Y, Jiang H, Han C, Zhang G, et al. HMGB1 Mediates Autophagy Dysfunction via Perturbing Beclin1-Vps34 Complex in Dopaminergic Cell Model. Front Mol Neurosci. 2017;10:13 pubmed publisher
    ..in autophagy dysfunction induced by ?-synuclein accumulation, and the Beclin1-vacuolar protein sorting 34 (Vps34) complex is of great importance to the initiation of autophagy...
  54. Cheng X, Ma X, Ding X, Li L, Jiang X, Shen Z, et al. Pacer Mediates the Function of Class III PI3K and HOPS Complexes in Autophagosome Maturation by Engaging Stx17. Mol Cell. 2017;65:1029-1043.e5 pubmed publisher
    ..Mechanistically, Pacer antagonizes Rubicon to stimulate Vps34 kinase activity...
  55. Maejima Y, Isobe M, Sadoshima J. Regulation of autophagy by Beclin 1 in the heart. J Mol Cell Cardiol. 2016;95:19-25 pubmed publisher
    ..component of the autophagy machinery, plays a central role in the regulation of autophagy through activation of Vps34. Beclin 1's ability to activate Vps34 is tightly regulated via transcriptional regulation, miRNA, post-..
  56. Hassett M, Sternberg A, Riegel B, Thomas C, Roepe P. Heterologous Expression, Purification, and Functional Analysis of Plasmodium falciparum Phosphatidylinositol 3'-Kinase. Biochemistry. 2017;56:4335-4345 pubmed publisher
    ..one phosphatidylinositol 3'-kinase (PI3K), and sequence analysis suggests that the enzyme is a "class III"- or "Vps34"-type PI3K...
  57. New J, Arnold L, Ananth M, Alvi S, Thornton M, Werner L, et al. Secretory Autophagy in Cancer-Associated Fibroblasts Promotes Head and Neck Cancer Progression and Offers a Novel Therapeutic Target. Cancer Res. 2017;77:6679-6691 pubmed publisher
    ..In a mouse xenograft model of HNSCC, pharmacologic inhibition of Vps34, a key mediator of autophagy, enhanced the antitumor efficacy of cisplatin...
  58. Koyasu S. The role of PI3K in immune cells. Nat Immunol. 2003;4:313-9 pubmed
    ..The development of gene-targeted mice now enables us to examine the physiological functions of individual PI3K enzymes in the immune system in vivo. ..
  59. Borgatti P, Zauli G, Colamussi M, Gibellini D, Previati M, Cantley L, et al. Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells. Eur J Immunol. 1997;27:2805-11 pubmed
    ..Taken together, these data suggest that the anti-apoptotic activity of low concentrations of Tat protein on Jurkat cells is mediated by a PI 3-kinase/Akt pathway. ..
  60. Baskaran S, Carlson L, Stjepanovic G, Young L, Kim D, Grob P, et al. Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex. elife. 2014;3: pubmed publisher
    ..phosphatidylinositol 3-kinase complex I (PI3KC3-C1) that functions in early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14...
  61. Valet C, Severin S, Chicanne G, Laurent P, Gaits Iacovoni F, Gratacap M, et al. The role of class I, II and III PI 3-kinases in platelet production and activation and their implication in thrombosis. Adv Biol Regul. 2016;61:33-41 pubmed publisher
    ..The role of class II PI3Kα and β as well as class III PI3K (Vps34) in platelet production and function is just emerging...
  62. Milani D, Mazzoni M, Borgatti P, Zauli G, Cantley L, Capitani S. Extracellular human immunodeficiency virus type-1 Tat protein activates phosphatidylinositol 3-kinase in PC12 neuronal cells. J Biol Chem. 1996;271:22961-4 pubmed
    ..Our data strongly support the concept that extracellular Tat acts as a cell stimulator, inducing intracellular signal transduction in uninfected cells. ..
  63. Jauliac S, Mazerolles F, Jabado N, Pallier A, Bernard F, Peake J, et al. Ligands of CD4 inhibit the association of phospholipase Cgamma1 with phosphoinositide 3 kinase in T cells: regulation of this association by the phosphoinositide 3 kinase activity. Eur J Immunol. 1998;28:3183-91 pubmed
    ..We propose that the products of the PI3 kinase are important mediators of the negative signaling induced by the binding of CD4 ligands to the CD4 molecule implicated in the regulation of the formation of multifunctional complexes. ..
  64. Lee C, Tomkowicz B, Freedman B, Collman R. HIV-1 gp120-induced TNF-{alpha} production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways. J Leukoc Biol. 2005;78:1016-23 pubmed
    ..These gp120-triggered signaling pathways may be responsible for inappropriate production of proinflammatory cytokines by macrophages, which are believed to play a role in immunopathogenesis and in neurological sequelae of AIDS. ..
  65. Zeng X, Overmeyer J, Maltese W. Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking. J Cell Sci. 2006;119:259-70 pubmed
    ..Immunoprecipitates of endogenous Beclin 1 contained human Vps34 (hVps34), but not Bcl-2...
  66. Trincheri N, Follo C, Nicotra G, Peracchio C, Castino R, Isidoro C. Resveratrol-induced apoptosis depends on the lipid kinase activity of Vps34 and on the formation of autophagolysosomes. Carcinogenesis. 2008;29:381-9 pubmed
    ..The present data also indicate that genetic or epigenetic inactivation of autophagy proteins in cancer cells may confer resistance to RV-mediated killing. ..
  67. Cheung R, Ravyn V, Wang L, Ptasznik A, Collman R. Signaling mechanism of HIV-1 gp120 and virion-induced IL-1beta release in primary human macrophages. J Immunol. 2008;180:6675-84 pubmed
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