DOI: 10.1083/jcb.152.3.519. Two Distinct Vps34 Phosphatidylinositol 3–Kinase Complexes Function in Autophagy and Carboxypeptidase Y Sorting in<i>Saccharomyces cerevisiae</i>

Two Distinct Vps34 Phosphatidylinositol 3–Kinase Complexes Function in Autophagy and Carboxypeptidase Y Sorting inSaccharomyces cerevisiae

10.1083/jcb.152.3.519

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Vps30p/Apg6p is required for both autophagy and sorting of carboxypeptidase Y (CPY). Although Vps30p is known to interact with Apg14p, its precise role remains unclear. We found that two proteins copurify with Vps30p. They were identified by mass spectrometry to be Vps38p and Vps34p, a phosphatidylinositol (PtdIns) 3–kinase. Vps34p, Vps38p, Apg14p, and Vps15p, an activator of Vps34p, were coimmunoprecipitated with Vps30p. These results indicate that Vps30p functions as a subunit of a Vps34 PtdIns 3–kinase complex(es). Phenotypic analyses indicated that Apg14p and Vps38p are each required for autophagy and CPY sorting, respectively, whereas Vps30p, Vps34p, and Vps15p are required for both processes. Coimmunoprecipitation using anti-Apg14p and anti-Vps38p antibodies and pull-down experiments showed that two distinct Vps34 PtdIns 3–kinase complexes exist: one, containing Vps15p, Vps30p, and Apg14p, functions in autophagy and the other containing Vps15p, Vps30p, and Vps38p functions in CPY sorting. The vps34 and vps15 mutants displayed additional phenotypes such as defects in transport of proteinase A and proteinase B, implying the existence of another PtdIns 3–kinase complex(es). We propose that multiple Vps34p–Vps15p complexes associated with specific regulatory proteins might fulfill their membrane trafficking events at different sites.

Bibliography

Kihara, A., Noda, T., Ishihara, N., & Ohsumi, Y. (2001). Two Distinct Vps34 Phosphatidylinositol 3âKinase Complexes Function in Autophagy and Carboxypeptidase Y Sorting inSaccharomyces cerevisiae. The Journal of Cell Biology, 152(3), 519â530.

Authors 4

Akio Kihara (first)
Takeshi Noda (additional)
Naotada Ishihara (additional)
Yoshinori Ohsumi (additional)

References 51 Referenced 830

10.1083/jcb.124.6.903 / J. Cell Biol. / Ultrastructural analysis of the autophagic process in yeastdetection of autophagosomes and their characterization by Baba (1994)
10.1083/jcb.139.7.1687 / J. Cell Biol. / Two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome by Baba (1997)
10.1073/pnas.92.18.8259 / Proc. Natl. Acad. Sci. USA / Predicting coiled coils by use of pairwise residue correlations by Berger (1995)
10.1083/jcb.130.4.781 / J. Cell Biol. / Role for phosphatidylinositol 3–kinase in the sorting and transport of newly synthesized lysosomal enzymes in mammalian cells by Brown (1995)
10.1016/S1097-2765(00)80125-2 / Mol. Cell / Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains by Burd (1998)
10.1016/0378-1119(92)90454-W / Gene / Multifunctional yeast high-copy-number shuttle vectors by Christianson (1992)
10.1083/jcb.133.3.529 / J. Cell Biol. / Vps10p cycles between the late-Golgi and prevacuolar compartments in its function as the sorting receptor for multiple yeast vacuolar hydrolases by Cooper (1996)
10.1083/jcb.130.4.797 / J. Cell Biol. / Wortmannin causes mistargeting of procathepsin D. Evidence for the involvement of a phosphatidylinositol 3–kinase in vesicular transport to lysosomes by Davidson (1995)
10.1016/0962-8924(94)90069-8 / Trends Cell Biol. / Autophagy and related mechanisms of lysosome-mediated protein degradation by Dunn (1994)
10.1074/jbc.272.39.24170 / J. Biol. Chem. / Inhibition of calcium-independent mannose 6-phosphate receptor incorporation into trans-Golgi network-derived clathrin-coated vesicles by wortmannin by Gaffet (1997)
10.1083/jcb.146.4.755 / J. Cell Biol. / Phosphoinositide–AP-2 interactions required for targeting to plasma membrane clathrin–coated pits by Gaidarov (1999)
10.1093/emboj/18.4.871 / EMBO (Eur. Mol. Biol. Organ.) J. / Arrestin function in G protein-coupled receptor endocytosis requires phosphoinositide binding by Gaidarov (1999)
10.1074/jbc.271.30.17621 / J. Biol. Chem. / Genetic and phenotypic overlap between autophagy and the cytoplasm to vacuole protein targeting pathway by Harding (1996)
{'key': '2023072211300949500_HermanandEmr1990', 'first-page': '6742', 'article-title': 'Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae', 'volume': '10', 'author': 'Herman', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae by Herman (1990)
10.1016/0092-8674(91)90650-N / Cell / A novel protein kinase homologue essential for protein sorting to the yeast lysosome-like vacuole by Herman (1991)
10.1002/j.1460-2075.1991.tb04981.x / EMBO (Eur. Mol. Biol. Organ.) J. / A genetic and structural analysis of the yeast Vps15 protein kinaseevidence for a direct role of Vps15p in vacuolar protein delivery by Herman (1991)
10.1016/0955-0674(95)80012-3 / Curr. Opin. Cell Biol. / Protein transport to the yeast vacuole by Horazdovsky (1995)
{'key': '2023072211300949500_Irieetal1993', 'first-page': '3076', 'article-title': 'MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase-kinase homologues, function in the pathway mediated by protein kinase C', 'volume': '13', 'author': 'Irie', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase-kinase homologues, function in the pathway mediated by protein kinase C by Irie (1993)
10.1074/jbc.273.35.22284 / J. Biol. Chem. / Apg14p and Apg6p/Vps30p form a protein complex essential for autophagy in the yeast, Saccharomyces cerevisiae by Kametaka (1998)
10.1002/(SICI)1097-0061(19990630)15:9<741::AID-YEA416>3.0.CO;2-O / Yeast / The Hansenula polymorpha PDD1 gene product, essential for the selective degradation of peroxisomes, is a homologue of Saccharomyces cerevisiae Vps34p by Kiel (1999)
10.1091/mbc.10.5.1337 / Mol. Biol. Cell / Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways by Kim (1999)
10.1083/jcb.147.2.435 / J. Cell Biol. / Formation process of autophagosome is traced with Apg8p/Aut7p in yeast by Kirisako (1999)
10.1146/annurev.cellbio.15.1.1 / Annu. Rev. Cell Dev. Biol. / Vacuolar import of proteins and organelles from the cytoplasm by Klionsky (1999)
10.1126/science.1862342 / Science / Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase by Knighton (1991)
10.1083/jcb.138.4.731 / J. Cell Biol. / Novel genes involved in endosomal traffic in yeast revealed by suppression of a targeting-defective plasma membrane ATPase mutant by Luo (1997)
10.1016/0092-8674(94)90219-4 / Cell / The sorting receptor for yeast vacuolar carboxypeptidase Y is encoded by the VPS10 gene by Marcusson (1994)
10.1083/jcb.127.2.373 / J. Cell Biol. / Endocytosis is required for the growth of vacuolar H+-ATPase–defective yeastidentification of six new END genes by Munn (1994)
10.1074/jbc.273.7.3963 / J. Biol. Chem. / Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast by Noda (1998)
10.1006/bbrc.1995.1636 / Biochem. Biophys. Res. Commun. / Novel system for monitoring autophagy in the yeast Saccharomyces cerevisiae by Noda (1995)
10.1083/jcb.148.3.465 / J. Cell Biol. / Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways by Noda (2000)
10.1074/jbc.272.4.2477 / J. Biol. Chem. / Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3–kinase by Panaretou (1997)
10.1016/S0960-9822(99)80071-2 / Curr. Biol. / Vac1p coordinates Rab and phosphatidylinositol 3–kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome by Peterson (1999)
10.1074/jbc.275.2.992 / J. Biol. Chem. / Distinct classes of phosphatidylinositol 3′-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells by Petiot (2000)
10.1083/jcb.131.3.603 / J. Cell Biol. / VPS27 controls vacuolar and endocytic traffic through a prevacuolar compartment in Saccharomyces cerevisiae by Piper (1995)
10.1091/mbc.3.12.1389 / Mol. Biol. Cell / Morphological classification of the yeast vacuolar protein sorting mutantsevidence for a prevacuolar compartment in class E vps mutants by Raymond (1992)
{'key': '2023072211300949500_Robinsonetal1988', 'first-page': '4936', 'article-title': 'Protein sorting in Saccharomyces cerevisiaeisolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases', 'volume': '8', 'author': 'Robinson', 'year': '1988', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Protein sorting in Saccharomyces cerevisiaeisolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases by Robinson (1988)
10.1126/science.8385367 / Science / Phosphatidylinositol 3–kinase encoded by yeast VPS34 gene essential for protein sorting by Schu (1993)
10.1073/pnas.93.22.12304 / Proc. Natl. Acad. Sci. USA / Cytoplasm-to-vacuole targeting and autophagy employ the same machinary to deliver proteins to the yeast vacuole by Scott (1996)
10.1083/jcb.137.1.79 / J. Cell Biol. / Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products by Seaman (1997)
10.1093/emboj/18.19.5234 / EMBO (Eur. Mol. Biol. Organ.) J. / Apg10p, a novel protein-conjugating enzyme essential for autophagy in yeast by Shintani (1999)
10.1093/genetics/122.1.19 / Genetics / A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae by Sikorski (1989)
10.1002/j.1460-2075.1993.tb05867.x / EMBO (Eur. Mol. Biol. Organ.) J. / 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 by Stack (1993)
10.1083/jcb.129.2.321 / J. Cell Biol. / Vesicle-mediated protein transportregulatory interactions between the Vps15 protein kinase and the Vps34 PtdIns 3–kinase essential for protein sorting to the vacuole in yeast by Stack (1995)
10.1091/mbc.10.6.1873 / Mol. Biol. Cell / The phosphatidylinositol 3-phosphate binding protein Vac1p interacts with a Rab GTPase and a Sec1p homologue to facilitate vesicle-mediated vacuolar protein sorting by Tall (1999)
10.1016/0014-5793(94)00672-5 / FEBS Lett. / Isolation of autophagocytosis mutants of Saccharomyces cerevisiae by Thumm (1994)
10.1016/0014-5793(93)80398-E / FEBS Lett. / Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae by Tsukada (1993)
10.1083/jcb.140.1.61 / J. Cell Biol. / A vacuolar v-t-SNARE complex, the predominant form in vivo and on isolated vacuoles, is disassembled and activated for docking and fusion by Ungermann (1998)
10.1083/jcb.146.1.85 / J. Cell Biol. / A cell-free assay allows reconstitution of Vps33p-dependent transport to the yeast vacuole/lysosome by Vida (1999)
10.1002/j.1460-2075.1995.tb07340.x / EMBO (Eur. Mol. Biol. Organ.) J. / A human phosphatidylinositol 3–kinase complex related to the yeast Vps34p-Vps15p protein sorting system by Volinia (1995)
10.1073/pnas.88.20.9184 / Proc. Natl. Acad. Sci. USA / Formation of phosphatidylinositol 3-phosphate by isomerization from phosphatidylinositol 4-phosphate by Walsh (1991)
10.1074/jbc.271.16.9429 / J. Biol. Chem. / Pro-ompA derivatives with a His6 tag in their N-terminal “translocation initiation domains” are arrested by Ni2+ at an early post-targeting stage of translocation by Yoshihisa (1996)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:46 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 7:30 a.m.)
Indexed	3 days, 3 hours ago (Aug. 29, 2025, 6:43 a.m.)
Issued	24 years, 7 months ago (Jan. 29, 2001)
Published	24 years, 7 months ago (Jan. 29, 2001)
Published Online	24 years, 7 months ago (Jan. 29, 2001)
Published Print	24 years, 6 months ago (Feb. 5, 2001)

Funders 0

None

BibTeX

@article{Kihara_2001, title={Two Distinct Vps34 Phosphatidylinositol 3–Kinase Complexes Function in Autophagy and Carboxypeptidase Y Sorting inSaccharomyces cerevisiae}, volume={152}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.152.3.519}, DOI={10.1083/jcb.152.3.519}, number={3}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Kihara, Akio and Noda, Takeshi and Ishihara, Naotada and Ohsumi, Yoshinori}, year={2001}, month=jan, pages={519–530} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        29
      ]
    ],
    "date-time": "2025-08-29T10:43:34Z",
    "timestamp": 1756464214763
  },
  "reference-count": 51,
  "publisher": "Rockefeller University Press",
  "issue": "3",
  "content-domain": {
    "domain": [
      "rupress.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2001,
        2,
        5
      ]
    ]
  },
  "abstract": "<jats:p>Vps30p/Apg6p is required for both autophagy and sorting of carboxypeptidase Y (CPY). Although Vps30p is known to interact with Apg14p, its precise role remains unclear. We found that two proteins copurify with Vps30p. They were identified by mass spectrometry to be Vps38p and Vps34p, a phosphatidylinositol (PtdIns) 3\u2013kinase. Vps34p, Vps38p, Apg14p, and Vps15p, an activator of Vps34p, were coimmunoprecipitated with Vps30p. These results indicate that Vps30p functions as a subunit of a Vps34 PtdIns 3\u2013kinase complex(es). Phenotypic analyses indicated that Apg14p and Vps38p are each required for autophagy and CPY sorting, respectively, whereas Vps30p, Vps34p, and Vps15p are required for both processes. Coimmunoprecipitation using anti-Apg14p and anti-Vps38p antibodies and pull-down experiments showed that two distinct Vps34 PtdIns 3\u2013kinase complexes exist: one, containing Vps15p, Vps30p, and Apg14p, functions in autophagy and the other containing Vps15p, Vps30p, and Vps38p functions in CPY sorting. The vps34 and vps15 mutants displayed additional phenotypes such as defects in transport of proteinase A and proteinase B, implying the existence of another PtdIns 3\u2013kinase complex(es). We propose that multiple Vps34p\u2013Vps15p complexes associated with specific regulatory proteins might fulfill their membrane trafficking events at different sites.</jats:p>",
  "DOI": "10.1083/jcb.152.3.519",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T16:46:23Z",
    "timestamp": 1027701983000
  },
  "page": "519-530",
  "update-policy": "http://dx.doi.org/10.1083/jcb.crossmarkpolicy",
  "source": "Crossref",
  "is-referenced-by-count": 830,
  "title": "Two Distinct Vps34 Phosphatidylinositol 3\u2013Kinase Complexes Function in Autophagy and Carboxypeptidase Y Sorting in<i>Saccharomyces cerevisiae</i>",
  "prefix": "10.1083",
  "volume": "152",
  "author": [
    {
      "given": "Akio",
      "family": "Kihara",
      "sequence": "first",
      "affiliation": [
        {
          "name": "aDepartment of Cell Biology, National Institute for Basic Biology, Okazaki, 444-8585, Japan"
        }
      ]
    },
    {
      "given": "Takeshi",
      "family": "Noda",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "aDepartment of Cell Biology, National Institute for Basic Biology, Okazaki, 444-8585, Japan"
        }
      ]
    },
    {
      "given": "Naotada",
      "family": "Ishihara",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "aDepartment of Cell Biology, National Institute for Basic Biology, Okazaki, 444-8585, Japan"
        }
      ]
    },
    {
      "given": "Yoshinori",
      "family": "Ohsumi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "aDepartment of Cell Biology, National Institute for Basic Biology, Okazaki, 444-8585, Japan"
        }
      ]
    }
  ],
  "member": "291",
  "published-online": {
    "date-parts": [
      [
        2001,
        1,
        29
      ]
    ]
  },
  "reference": [
    {
      "key": "2023072211300949500_Babaetal1994",
      "doi-asserted-by": "crossref",
      "first-page": "903",
      "DOI": "10.1083/jcb.124.6.903",
      "article-title": "Ultrastructural analysis of the autophagic process in yeastdetection of autophagosomes and their characterization",
      "volume": "124",
      "author": "Baba",
      "year": "1994",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Babaetal1997",
      "doi-asserted-by": "crossref",
      "first-page": "1687",
      "DOI": "10.1083/jcb.139.7.1687",
      "article-title": "Two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome",
      "volume": "139",
      "author": "Baba",
      "year": "1997",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Bergeretal1995",
      "doi-asserted-by": "crossref",
      "first-page": "8259",
      "DOI": "10.1073/pnas.92.18.8259",
      "article-title": "Predicting coiled coils by use of pairwise residue correlations",
      "volume": "92",
      "author": "Berger",
      "year": "1995",
      "journal-title": "Proc. Natl. Acad. Sci. USA"
    },
    {
      "key": "2023072211300949500_Brownetal1995",
      "doi-asserted-by": "crossref",
      "first-page": "781",
      "DOI": "10.1083/jcb.130.4.781",
      "article-title": "Role for phosphatidylinositol 3\u2013kinase in the sorting and transport of newly synthesized lysosomal enzymes in mammalian cells",
      "volume": "130",
      "author": "Brown",
      "year": "1995",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_BurdandEmr1998",
      "doi-asserted-by": "crossref",
      "first-page": "157",
      "DOI": "10.1016/S1097-2765(00)80125-2",
      "article-title": "Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains",
      "volume": "2",
      "author": "Burd",
      "year": "1998",
      "journal-title": "Mol. Cell"
    },
    {
      "key": "2023072211300949500_Christiansonetal1992",
      "doi-asserted-by": "crossref",
      "first-page": "119",
      "DOI": "10.1016/0378-1119(92)90454-W",
      "article-title": "Multifunctional yeast high-copy-number shuttle vectors",
      "volume": "110",
      "author": "Christianson",
      "year": "1992",
      "journal-title": "Gene"
    },
    {
      "key": "2023072211300949500_CooperandStevens1996",
      "doi-asserted-by": "crossref",
      "first-page": "529",
      "DOI": "10.1083/jcb.133.3.529",
      "article-title": "Vps10p cycles between the late-Golgi and prevacuolar compartments in its function as the sorting receptor for multiple yeast vacuolar hydrolases",
      "volume": "133",
      "author": "Cooper",
      "year": "1996",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Davidson1995",
      "doi-asserted-by": "crossref",
      "first-page": "797",
      "DOI": "10.1083/jcb.130.4.797",
      "article-title": "Wortmannin causes mistargeting of procathepsin D. Evidence for the involvement of a phosphatidylinositol 3\u2013kinase in vesicular transport to lysosomes",
      "volume": "130",
      "author": "Davidson",
      "year": "1995",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Dunn1994",
      "doi-asserted-by": "crossref",
      "first-page": "139",
      "DOI": "10.1016/0962-8924(94)90069-8",
      "article-title": "Autophagy and related mechanisms of lysosome-mediated protein degradation",
      "volume": "4",
      "author": "Dunn",
      "year": "1994",
      "journal-title": "Trends Cell Biol."
    },
    {
      "key": "2023072211300949500_Gaffetetal1997",
      "doi-asserted-by": "crossref",
      "first-page": "24170",
      "DOI": "10.1074/jbc.272.39.24170",
      "article-title": "Inhibition of calcium-independent mannose 6-phosphate receptor incorporation into trans-Golgi network-derived clathrin-coated vesicles by wortmannin",
      "volume": "272",
      "author": "Gaffet",
      "year": "1997",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072211300949500_GaidarovandKeen1999",
      "doi-asserted-by": "crossref",
      "first-page": "755",
      "DOI": "10.1083/jcb.146.4.755",
      "article-title": "Phosphoinositide\u2013AP-2 interactions required for targeting to plasma membrane clathrin\u2013coated pits",
      "volume": "146",
      "author": "Gaidarov",
      "year": "1999",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Gaidarovetal1999",
      "doi-asserted-by": "crossref",
      "first-page": "871",
      "DOI": "10.1093/emboj/18.4.871",
      "article-title": "Arrestin function in G protein-coupled receptor endocytosis requires phosphoinositide binding",
      "volume": "18",
      "author": "Gaidarov",
      "year": "1999",
      "journal-title": "EMBO (Eur. Mol. Biol. Organ.) J."
    },
    {
      "key": "2023072211300949500_Hardingetal1996",
      "doi-asserted-by": "crossref",
      "first-page": "17621",
      "DOI": "10.1074/jbc.271.30.17621",
      "article-title": "Genetic and phenotypic overlap between autophagy and the cytoplasm to vacuole protein targeting pathway",
      "volume": "271",
      "author": "Harding",
      "year": "1996",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072211300949500_HermanandEmr1990",
      "first-page": "6742",
      "article-title": "Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae",
      "volume": "10",
      "author": "Herman",
      "year": "1990",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072211300949500_Hermanetal1991a",
      "doi-asserted-by": "crossref",
      "first-page": "425",
      "DOI": "10.1016/0092-8674(91)90650-N",
      "article-title": "A novel protein kinase homologue essential for protein sorting to the yeast lysosome-like vacuole",
      "volume": "64",
      "author": "Herman",
      "year": "1991",
      "journal-title": "Cell"
    },
    {
      "key": "2023072211300949500_Hermanetal1991b",
      "doi-asserted-by": "crossref",
      "first-page": "4049",
      "DOI": "10.1002/j.1460-2075.1991.tb04981.x",
      "article-title": "A genetic and structural analysis of the yeast Vps15 protein kinaseevidence for a direct role of Vps15p in vacuolar protein delivery",
      "volume": "10",
      "author": "Herman",
      "year": "1991",
      "journal-title": "EMBO (Eur. Mol. Biol. Organ.) J."
    },
    {
      "key": "2023072211300949500_Horazdovskyetal1995",
      "doi-asserted-by": "crossref",
      "first-page": "544",
      "DOI": "10.1016/0955-0674(95)80012-3",
      "article-title": "Protein transport to the yeast vacuole",
      "volume": "7",
      "author": "Horazdovsky",
      "year": "1995",
      "journal-title": "Curr. Opin. Cell Biol."
    },
    {
      "key": "2023072211300949500_Irieetal1993",
      "first-page": "3076",
      "article-title": "MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase-kinase homologues, function in the pathway mediated by protein kinase C",
      "volume": "13",
      "author": "Irie",
      "year": "1993",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072211300949500_Kametakaetal1998",
      "doi-asserted-by": "crossref",
      "first-page": "22284",
      "DOI": "10.1074/jbc.273.35.22284",
      "article-title": "Apg14p and Apg6p/Vps30p form a protein complex essential for autophagy in the yeast, Saccharomyces cerevisiae",
      "volume": "273",
      "author": "Kametaka",
      "year": "1998",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072211300949500_Kieletal1999",
      "doi-asserted-by": "crossref",
      "first-page": "741",
      "DOI": "10.1002/(SICI)1097-0061(19990630)15:9<741::AID-YEA416>3.0.CO;2-O",
      "article-title": "The Hansenula polymorpha PDD1 gene product, essential for the selective degradation of peroxisomes, is a homologue of Saccharomyces cerevisiae Vps34p",
      "volume": "15",
      "author": "Kiel",
      "year": "1999",
      "journal-title": "Yeast"
    },
    {
      "key": "2023072211300949500_Kimetal1999",
      "doi-asserted-by": "crossref",
      "first-page": "1337",
      "DOI": "10.1091/mbc.10.5.1337",
      "article-title": "Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways",
      "volume": "10",
      "author": "Kim",
      "year": "1999",
      "journal-title": "Mol. Biol. Cell"
    },
    {
      "key": "2023072211300949500_Kirisakoetal1999",
      "doi-asserted-by": "crossref",
      "first-page": "435",
      "DOI": "10.1083/jcb.147.2.435",
      "article-title": "Formation process of autophagosome is traced with Apg8p/Aut7p in yeast",
      "volume": "147",
      "author": "Kirisako",
      "year": "1999",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_KlionskyandOhsumi1999",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.1146/annurev.cellbio.15.1.1",
      "article-title": "Vacuolar import of proteins and organelles from the cytoplasm",
      "volume": "15",
      "author": "Klionsky",
      "year": "1999",
      "journal-title": "Annu. Rev. Cell Dev. Biol."
    },
    {
      "key": "2023072211300949500_Knightonetal1991",
      "doi-asserted-by": "crossref",
      "first-page": "407",
      "DOI": "10.1126/science.1862342",
      "article-title": "Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase",
      "volume": "253",
      "author": "Knighton",
      "year": "1991",
      "journal-title": "Science"
    },
    {
      "key": "2023072211300949500_LuoandChang1997",
      "doi-asserted-by": "crossref",
      "first-page": "731",
      "DOI": "10.1083/jcb.138.4.731",
      "article-title": "Novel genes involved in endosomal traffic in yeast revealed by suppression of a targeting-defective plasma membrane ATPase mutant",
      "volume": "138",
      "author": "Luo",
      "year": "1997",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Marcussonetal1994",
      "doi-asserted-by": "crossref",
      "first-page": "579",
      "DOI": "10.1016/0092-8674(94)90219-4",
      "article-title": "The sorting receptor for yeast vacuolar carboxypeptidase Y is encoded by the VPS10 gene",
      "volume": "77",
      "author": "Marcusson",
      "year": "1994",
      "journal-title": "Cell"
    },
    {
      "key": "2023072211300949500_MunnandRiezman1994",
      "doi-asserted-by": "crossref",
      "first-page": "373",
      "DOI": "10.1083/jcb.127.2.373",
      "article-title": "Endocytosis is required for the growth of vacuolar H+-ATPase\u2013defective yeastidentification of six new END genes",
      "volume": "127",
      "author": "Munn",
      "year": "1994",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_NodaandOhsumi1998",
      "doi-asserted-by": "crossref",
      "first-page": "3963",
      "DOI": "10.1074/jbc.273.7.3963",
      "article-title": "Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast",
      "volume": "273",
      "author": "Noda",
      "year": "1998",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072211300949500_Nodaetal1995",
      "doi-asserted-by": "crossref",
      "first-page": "126",
      "DOI": "10.1006/bbrc.1995.1636",
      "article-title": "Novel system for monitoring autophagy in the yeast Saccharomyces cerevisiae",
      "volume": "210",
      "author": "Noda",
      "year": "1995",
      "journal-title": "Biochem. Biophys. Res. Commun."
    },
    {
      "key": "2023072211300949500_Nodaetal2000",
      "doi-asserted-by": "crossref",
      "first-page": "465",
      "DOI": "10.1083/jcb.148.3.465",
      "article-title": "Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways",
      "volume": "148",
      "author": "Noda",
      "year": "2000",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Panaretouetal1997",
      "doi-asserted-by": "crossref",
      "first-page": "2477",
      "DOI": "10.1074/jbc.272.4.2477",
      "article-title": "Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3\u2013kinase",
      "volume": "272",
      "author": "Panaretou",
      "year": "1997",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072211300949500_Petersonetal1999",
      "doi-asserted-by": "crossref",
      "first-page": "159",
      "DOI": "10.1016/S0960-9822(99)80071-2",
      "article-title": "Vac1p coordinates Rab and phosphatidylinositol 3\u2013kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome",
      "volume": "9",
      "author": "Peterson",
      "year": "1999",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "2023072211300949500_Petiotetal2000",
      "doi-asserted-by": "crossref",
      "first-page": "992",
      "DOI": "10.1074/jbc.275.2.992",
      "article-title": "Distinct classes of phosphatidylinositol 3\u2032-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells",
      "volume": "275",
      "author": "Petiot",
      "year": "2000",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072211300949500_Piperetal1995",
      "doi-asserted-by": "crossref",
      "first-page": "603",
      "DOI": "10.1083/jcb.131.3.603",
      "article-title": "VPS27 controls vacuolar and endocytic traffic through a prevacuolar compartment in Saccharomyces cerevisiae",
      "volume": "131",
      "author": "Piper",
      "year": "1995",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Raymondetal1992",
      "doi-asserted-by": "crossref",
      "first-page": "1389",
      "DOI": "10.1091/mbc.3.12.1389",
      "article-title": "Morphological classification of the yeast vacuolar protein sorting mutantsevidence for a prevacuolar compartment in class E vps mutants",
      "volume": "3",
      "author": "Raymond",
      "year": "1992",
      "journal-title": "Mol. Biol. Cell"
    },
    {
      "key": "2023072211300949500_Robinsonetal1988",
      "first-page": "4936",
      "article-title": "Protein sorting in Saccharomyces cerevisiaeisolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases",
      "volume": "8",
      "author": "Robinson",
      "year": "1988",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072211300949500_Schuetal1993",
      "doi-asserted-by": "crossref",
      "first-page": "88",
      "DOI": "10.1126/science.8385367",
      "article-title": "Phosphatidylinositol 3\u2013kinase encoded by yeast VPS34 gene essential for protein sorting",
      "volume": "260",
      "author": "Schu",
      "year": "1993",
      "journal-title": "Science"
    },
    {
      "key": "2023072211300949500_Scottetal1996",
      "doi-asserted-by": "crossref",
      "first-page": "12304",
      "DOI": "10.1073/pnas.93.22.12304",
      "article-title": "Cytoplasm-to-vacuole targeting and autophagy employ the same machinary to deliver proteins to the yeast vacuole",
      "volume": "93",
      "author": "Scott",
      "year": "1996",
      "journal-title": "Proc. Natl. Acad. Sci. USA"
    },
    {
      "key": "2023072211300949500_Seamanetal1997",
      "doi-asserted-by": "crossref",
      "first-page": "79",
      "DOI": "10.1083/jcb.137.1.79",
      "article-title": "Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products",
      "volume": "137",
      "author": "Seaman",
      "year": "1997",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Shintanietal1999",
      "doi-asserted-by": "crossref",
      "first-page": "5234",
      "DOI": "10.1093/emboj/18.19.5234",
      "article-title": "Apg10p, a novel protein-conjugating enzyme essential for autophagy in yeast",
      "volume": "18",
      "author": "Shintani",
      "year": "1999",
      "journal-title": "EMBO (Eur. Mol. Biol. Organ.) J."
    },
    {
      "key": "2023072211300949500_SikorskiandHieter1989",
      "doi-asserted-by": "crossref",
      "first-page": "19",
      "DOI": "10.1093/genetics/122.1.19",
      "article-title": "A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae",
      "volume": "122",
      "author": "Sikorski",
      "year": "1989",
      "journal-title": "Genetics"
    },
    {
      "key": "2023072211300949500_Stacketal1993",
      "doi-asserted-by": "crossref",
      "first-page": "2195",
      "DOI": "10.1002/j.1460-2075.1993.tb05867.x",
      "article-title": "A membrane-associated complex containing the Vps15 protein kinase and the Vps34 PI 3\u2013kinase is essential for protein sorting to the yeast lysosome-like vacuole",
      "volume": "12",
      "author": "Stack",
      "year": "1993",
      "journal-title": "EMBO (Eur. Mol. Biol. Organ.) J."
    },
    {
      "key": "2023072211300949500_Stacketal1995",
      "doi-asserted-by": "crossref",
      "first-page": "321",
      "DOI": "10.1083/jcb.129.2.321",
      "article-title": "Vesicle-mediated protein transportregulatory interactions between the Vps15 protein kinase and the Vps34 PtdIns 3\u2013kinase essential for protein sorting to the vacuole in yeast",
      "volume": "129",
      "author": "Stack",
      "year": "1995",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Talletal1999",
      "doi-asserted-by": "crossref",
      "first-page": "1873",
      "DOI": "10.1091/mbc.10.6.1873",
      "article-title": "The phosphatidylinositol 3-phosphate binding protein Vac1p interacts with a Rab GTPase and a Sec1p homologue to facilitate vesicle-mediated vacuolar protein sorting",
      "volume": "10",
      "author": "Tall",
      "year": "1999",
      "journal-title": "Mol. Biol. Cell"
    },
    {
      "key": "2023072211300949500_Thummetal1994",
      "doi-asserted-by": "crossref",
      "first-page": "275",
      "DOI": "10.1016/0014-5793(94)00672-5",
      "article-title": "Isolation of autophagocytosis mutants of Saccharomyces cerevisiae",
      "volume": "349",
      "author": "Thumm",
      "year": "1994",
      "journal-title": "FEBS Lett."
    },
    {
      "key": "2023072211300949500_TsukadaandOhsumi1993",
      "doi-asserted-by": "crossref",
      "first-page": "169",
      "DOI": "10.1016/0014-5793(93)80398-E",
      "article-title": "Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae",
      "volume": "333",
      "author": "Tsukada",
      "year": "1993",
      "journal-title": "FEBS Lett."
    },
    {
      "key": "2023072211300949500_Ungermannetal1998",
      "doi-asserted-by": "crossref",
      "first-page": "61",
      "DOI": "10.1083/jcb.140.1.61",
      "article-title": "A vacuolar v-t-SNARE complex, the predominant form in vivo and on isolated vacuoles, is disassembled and activated for docking and fusion",
      "volume": "140",
      "author": "Ungermann",
      "year": "1998",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_VidaandGerhardt1999",
      "doi-asserted-by": "crossref",
      "first-page": "85",
      "DOI": "10.1083/jcb.146.1.85",
      "article-title": "A cell-free assay allows reconstitution of Vps33p-dependent transport to the yeast vacuole/lysosome",
      "volume": "146",
      "author": "Vida",
      "year": "1999",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072211300949500_Voliniaetal1995",
      "doi-asserted-by": "crossref",
      "first-page": "3339",
      "DOI": "10.1002/j.1460-2075.1995.tb07340.x",
      "article-title": "A human phosphatidylinositol 3\u2013kinase complex related to the yeast Vps34p-Vps15p protein sorting system",
      "volume": "14",
      "author": "Volinia",
      "year": "1995",
      "journal-title": "EMBO (Eur. Mol. Biol. Organ.) J."
    },
    {
      "key": "2023072211300949500_Walshetal1991",
      "doi-asserted-by": "crossref",
      "first-page": "9184",
      "DOI": "10.1073/pnas.88.20.9184",
      "article-title": "Formation of phosphatidylinositol 3-phosphate by isomerization from phosphatidylinositol 4-phosphate",
      "volume": "88",
      "author": "Walsh",
      "year": "1991",
      "journal-title": "Proc. Natl. Acad. Sci. USA"
    },
    {
      "key": "2023072211300949500_YoshihisaandIto1996",
      "doi-asserted-by": "crossref",
      "first-page": "9429",
      "DOI": "10.1074/jbc.271.16.9429",
      "article-title": "Pro-ompA derivatives with a His6 tag in their N-terminal \u201ctranslocation initiation domains\u201d are arrested by Ni2+ at an early post-targeting stage of translocation",
      "volume": "271",
      "author": "Yoshihisa",
      "year": "1996",
      "journal-title": "J. Biol. Chem."
    }
  ],
  "container-title": "The Journal of Cell Biology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://rupress.org/jcb/article-pdf/152/3/519/1510122/0009133.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://rupress.org/jcb/article-pdf/152/3/519/1510122/0009133.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        7,
        22
      ]
    ],
    "date-time": "2023-07-22T11:30:52Z",
    "timestamp": 1690025452000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://rupress.org/jcb/article/152/3/519/45780/Two-Distinct-Vps34-Phosphatidylinositol-3-Kinase"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2001,
        1,
        29
      ]
    ]
  },
  "references-count": 51,
  "journal-issue": {
    "issue": "3",
    "published-print": {
      "date-parts": [
        [
          2001,
          2,
          5
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1083/jcb.152.3.519",
  "relation": {},
  "ISSN": [
    "0021-9525",
    "1540-8140"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2001,
        1,
        29
      ]
    ]
  }
}