RapamycinFungusV1, Main, Exploration, bibRecord, 000C05

Target of Rapamycin Complex 2 Regulates Actin Polarization and Endocytosis via Multiple Pathways.

Identifieur interne : 000C05 ( Main/Exploration ); précédent : 000C04; suivant : 000C06

Target of Rapamycin Complex 2 Regulates Actin Polarization and Endocytosis via Multiple Pathways.

Auteurs : Delphine Rispal [Suisse] ; Sandra Eltschinger [Suisse] ; Michael Stahl [Suisse] ; Stefania Vaga [Suisse] ; Bernd Bodenmiller [Suisse] ; Yann Abraham ; Ireos Filipuzzi ; N Rao Movva ; Ruedi Aebersold [Suisse] ; Stephen B. Helliwell [Oman] ; Robbie Loewith [Suisse]

Source :

The Journal of biological chemistry [ 1083-351X ] ; 2015.

RBID : pubmed:25882841

Descripteurs français

English descriptors

KwdEn :
- Actins (metabolism), Endocytosis (MeSH), Fungal Proteins (metabolism), Mechanistic Target of Rapamycin Complex 2 (MeSH), Multiprotein Complexes (physiology), Phosphorylation (MeSH), Principal Component Analysis (MeSH), Protein Kinases (metabolism), Proteomics (MeSH), Saccharomyces cerevisiae (metabolism), Saccharomyces cerevisiae Proteins (metabolism), Signal Transduction (MeSH), TOR Serine-Threonine Kinases (physiology).
MESH :
- chemical , metabolism : Actins, Fungal Proteins, Protein Kinases, Saccharomyces cerevisiae Proteins.
- chemical , physiology : Multiprotein Complexes, TOR Serine-Threonine Kinases.
- metabolism : Saccharomyces cerevisiae.
- Endocytosis, Mechanistic Target of Rapamycin Complex 2, Phosphorylation, Principal Component Analysis, Proteomics, Signal Transduction.

Abstract

Target of rapamycin is a Ser/Thr kinase that operates in two conserved multiprotein complexes, TORC1 and TORC2. Unlike TORC1, TORC2 is insensitive to rapamycin, and its functional characterization is less advanced. Previous genetic studies demonstrated that TORC2 depletion leads to loss of actin polarization and loss of endocytosis. To determine how TORC2 regulates these readouts, we engineered a yeast strain in which TORC2 can be specifically and acutely inhibited by the imidazoquinoline NVP-BHS345. Kinetic analyses following inhibition of TORC2, supported with quantitative phosphoproteomics, revealed that TORC2 regulates these readouts via distinct pathways as follows: rapidly through direct protein phosphorylation cascades and slowly through indirect changes in the tensile properties of the plasma membrane. The rapid signaling events are mediated in large part through the phospholipid flippase kinases Fpk1 and Fpk2, whereas the slow signaling pathway involves increased plasma membrane tension resulting from a gradual depletion of sphingolipids. Additional hits in our phosphoproteomic screens highlight the intricate control TORC2 exerts over diverse aspects of eukaryote cell physiology.

DOI: 10.1074/jbc.M114.627794
PubMed: 25882841
PubMed Central: PMC4463442

Affiliations:

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<series><title level="j">The Journal of biological chemistry</title>
<idno type="eISSN">1083-351X</idno>
<imprint><date when="2015" type="published">2015</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Actins (metabolism)</term>
<term>Endocytosis (MeSH)</term>
<term>Fungal Proteins (metabolism)</term>
<term>Mechanistic Target of Rapamycin Complex 2 (MeSH)</term>
<term>Multiprotein Complexes (physiology)</term>
<term>Phosphorylation (MeSH)</term>
<term>Principal Component Analysis (MeSH)</term>
<term>Protein Kinases (metabolism)</term>
<term>Proteomics (MeSH)</term>
<term>Saccharomyces cerevisiae (metabolism)</term>
<term>Saccharomyces cerevisiae Proteins (metabolism)</term>
<term>Signal Transduction (MeSH)</term>
<term>TOR Serine-Threonine Kinases (physiology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Actines (métabolisme)</term>
<term>Analyse en composantes principales (MeSH)</term>
<term>Complexe-2 cible mécanistique de la rapamycine (MeSH)</term>
<term>Complexes multiprotéiques (physiologie)</term>
<term>Endocytose (MeSH)</term>
<term>Phosphorylation (MeSH)</term>
<term>Protein kinases (métabolisme)</term>
<term>Protéines de Saccharomyces cerevisiae (métabolisme)</term>
<term>Protéines fongiques (métabolisme)</term>
<term>Protéomique (MeSH)</term>
<term>Saccharomyces cerevisiae (métabolisme)</term>
<term>Sérine-thréonine kinases TOR (physiologie)</term>
<term>Transduction du signal (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Actins</term>
<term>Fungal Proteins</term>
<term>Protein Kinases</term>
<term>Saccharomyces cerevisiae Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Multiprotein Complexes</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Actines</term>
<term>Protein kinases</term>
<term>Protéines de Saccharomyces cerevisiae</term>
<term>Protéines fongiques</term>
<term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Complexes multiprotéiques</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Endocytosis</term>
<term>Mechanistic Target of Rapamycin Complex 2</term>
<term>Phosphorylation</term>
<term>Principal Component Analysis</term>
<term>Proteomics</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Analyse en composantes principales</term>
<term>Complexe-2 cible mécanistique de la rapamycine</term>
<term>Endocytose</term>
<term>Phosphorylation</term>
<term>Protéomique</term>
<term>Transduction du signal</term>
</keywords>
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<front><div type="abstract" xml:lang="en">Target of rapamycin is a Ser/Thr kinase that operates in two conserved multiprotein complexes, TORC1 and TORC2. Unlike TORC1, TORC2 is insensitive to rapamycin, and its functional characterization is less advanced. Previous genetic studies demonstrated that TORC2 depletion leads to loss of actin polarization and loss of endocytosis. To determine how TORC2 regulates these readouts, we engineered a yeast strain in which TORC2 can be specifically and acutely inhibited by the imidazoquinoline NVP-BHS345. Kinetic analyses following inhibition of TORC2, supported with quantitative phosphoproteomics, revealed that TORC2 regulates these readouts via distinct pathways as follows: rapidly through direct protein phosphorylation cascades and slowly through indirect changes in the tensile properties of the plasma membrane. The rapid signaling events are mediated in large part through the phospholipid flippase kinases Fpk1 and Fpk2, whereas the slow signaling pathway involves increased plasma membrane tension resulting from a gradual depletion of sphingolipids. Additional hits in our phosphoproteomic screens highlight the intricate control TORC2 exerts over diverse aspects of eukaryote cell physiology. </div>
</front>
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<Month>09</Month>
<Day>10</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
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<Issue>24</Issue>
<PubDate><Year>2015</Year>
<Month>Jun</Month>
<Day>12</Day>
</PubDate>
</JournalIssue>
<Title>The Journal of biological chemistry</Title>
<ISOAbbreviation>J Biol Chem</ISOAbbreviation>
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<ArticleTitle>Target of Rapamycin Complex 2 Regulates Actin Polarization and Endocytosis via Multiple Pathways.</ArticleTitle>
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<Abstract><AbstractText>Target of rapamycin is a Ser/Thr kinase that operates in two conserved multiprotein complexes, TORC1 and TORC2. Unlike TORC1, TORC2 is insensitive to rapamycin, and its functional characterization is less advanced. Previous genetic studies demonstrated that TORC2 depletion leads to loss of actin polarization and loss of endocytosis. To determine how TORC2 regulates these readouts, we engineered a yeast strain in which TORC2 can be specifically and acutely inhibited by the imidazoquinoline NVP-BHS345. Kinetic analyses following inhibition of TORC2, supported with quantitative phosphoproteomics, revealed that TORC2 regulates these readouts via distinct pathways as follows: rapidly through direct protein phosphorylation cascades and slowly through indirect changes in the tensile properties of the plasma membrane. The rapid signaling events are mediated in large part through the phospholipid flippase kinases Fpk1 and Fpk2, whereas the slow signaling pathway involves increased plasma membrane tension resulting from a gradual depletion of sphingolipids. Additional hits in our phosphoproteomic screens highlight the intricate control TORC2 exerts over diverse aspects of eukaryote cell physiology. </AbstractText>
<CopyrightInformation>© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rispal</LastName>
<ForeName>Delphine</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>From the Department of Molecular Biology and Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 1211 Geneva.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Eltschinger</LastName>
<ForeName>Sandra</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>From the Department of Molecular Biology and Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 1211 Geneva.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Stahl</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>From the Department of Molecular Biology and Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 1211 Geneva.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Vaga</LastName>
<ForeName>Stefania</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>the Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bodenmiller</LastName>
<ForeName>Bernd</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>the Institute of Molecular Life Sciences, University of Zürich, 8057 Zürich.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Abraham</LastName>
<ForeName>Yann</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>the Novartis Institutes for Biomedical Research, Novartis Campus, 4056 Basel.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Filipuzzi</LastName>
<ForeName>Ireos</ForeName>
<Initials>I</Initials>
<AffiliationInfo><Affiliation>the Novartis Institutes for Biomedical Research, Novartis Campus, 4056 Basel.</Affiliation>
</AffiliationInfo>
</Author>
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	Serveur d'exploration sur la rapamycine et les champignons
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Serveur d'exploration sur la rapamycine et les champignons

Target of Rapamycin Complex 2 Regulates Actin Polarization and Endocytosis via Multiple Pathways.

Target of Rapamycin Complex 2 Regulates Actin Polarization and Endocytosis via Multiple Pathways.

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