March 11, 2014 Journal article Closed Access

Miguel Mano; Sergio Valente; Antonello Mai; Maria Ines Gutierrez; Mauro Giacca; Lucia Pattarini; Sergio Pantano; Annalisa Zecchin; Michael P. Myers

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  <identifier identifierType="URL">https://www.openaccessrepository.it/record/101067</identifier>
  <creators>
    <creator>
      <creatorName>Miguel Mano</creatorName>
    </creator>
    <creator>
      <creatorName>Sergio Valente</creatorName>
    </creator>
    <creator>
      <creatorName>Antonello Mai</creatorName>
    </creator>
    <creator>
      <creatorName>Maria Ines Gutierrez</creatorName>
    </creator>
    <creator>
      <creatorName>Mauro Giacca</creatorName>
    </creator>
    <creator>
      <creatorName>Lucia Pattarini</creatorName>
    </creator>
    <creator>
      <creatorName>Sergio Pantano</creatorName>
    </creator>
    <creator>
      <creatorName>Annalisa Zecchin</creatorName>
    </creator>
    <creator>
      <creatorName>Michael P. Myers</creatorName>
    </creator>
  </creators>
  <titles>
    <title>Reversible acetylation regulates vascular endothelial growth factor receptor-2 activity</title>
  </titles>
  <publisher>INFN Open Access Repository</publisher>
  <publicationYear>2014</publicationYear>
  <subjects>
    <subject>Health</subject>
    <subject>SP1-Cooperation</subject>
    <subject>ERC</subject>
    <subject>EC</subject>
    <subject>FP7</subject>
    <subject>SP2-Ideas</subject>
    <subject>European Commission</subject>
    <subject>Cell Biology</subject>
    <subject>Genetics</subject>
    <subject>Molecular Biology</subject>
    <subject>General Medicine</subject>
  </subjects>
  <dates>
    <date dateType="Issued">2014-03-11</date>
  </dates>
  <language>en</language>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://www.openaccessrepository.it/record/101067</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1093/jmcb/mju010</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://www.openaccessrepository.it/communities/itmirror</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="info:eu-repo/semantics/closedAccess">Closed Access</rights>
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  <descriptions>
    <description descriptionType="Abstract">The tyrosine kinase receptor vascular endothelial growth factor receptor 2 (VEGFR2) is a key regulator of angiogenesis. Here we show that VEGFR2 is acetylated in endothelial cells both at four lysine residues forming a dense cluster in the kinase insert domain and at a single lysine located in the receptor activation loop. These modifications are under dynamic control of the acetyltransferase p300 and two deacetylases HDAC5 and HDAC6. We demonstrate that VEGFR2 acetylation essentially regulates receptor phosphorylation. In particular, VEGFR2 acetylation significantly alters the kinetics of receptor phosphorylation after ligand binding, allowing receptor phosphorylation and intracellular signaling upon prolonged stimulation with VEGF. Molecular dynamics simulations indicate that acetylation of the lysine in the activation loop contributes to the transition to an open active state, in which tyrosine phosphorylation is favored by better exposure of the kinase target residues. These findings indicate that post-translational modification by acetylation is a critical mechanism that directly affects VEGFR2 function.</description>
  </descriptions>
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