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

MARC21 XML Export

<?xml version='1.0' encoding='UTF-8'?>
<record xmlns="http://www.loc.gov/MARC21/slim">
  <leader>00000nam##2200000uu#4500</leader>
  <datafield tag="650" ind1="1" ind2="7">
    <subfield code="a">cc-by</subfield>
    <subfield code="2">opendefinition.org</subfield>
  </datafield>
  <datafield tag="520" ind1=" " ind2=" ">
    <subfield code="a">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.</subfield>
  </datafield>
  <datafield tag="980" ind1=" " ind2=" ">
    <subfield code="a">user-itmirror</subfield>
  </datafield>
  <controlfield tag="001">101067</controlfield>
  <controlfield tag="005">20230925201413.0</controlfield>
  <datafield tag="041" ind1=" " ind2=" ">
    <subfield code="a">eng</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Sergio Valente</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Antonello Mai</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Maria Ines Gutierrez</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Mauro Giacca</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Lucia Pattarini</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Sergio Pantano</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Annalisa Zecchin</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Michael P. Myers</subfield>
  </datafield>
  <datafield tag="024" ind1=" " ind2=" ">
    <subfield code="a">10.1093/jmcb/mju010</subfield>
    <subfield code="2">doi</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">Health</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">SP1-Cooperation</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">ERC</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">EC</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">FP7</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">SP2-Ideas</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">European Commission</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">Cell Biology</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">Genetics</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">Molecular Biology</subfield>
  </datafield>
  <datafield tag="653" ind1=" " ind2=" ">
    <subfield code="a">General Medicine</subfield>
  </datafield>
  <datafield tag="100" ind1=" " ind2=" ">
    <subfield code="a">Miguel Mano</subfield>
  </datafield>
  <datafield tag="980" ind1=" " ind2=" ">
    <subfield code="a">publication</subfield>
    <subfield code="b">article</subfield>
  </datafield>
  <datafield tag="540" ind1=" " ind2=" ">
    <subfield code="a">Other (Open)</subfield>
  </datafield>
  <datafield tag="245" ind1=" " ind2=" ">
    <subfield code="a">Reversible acetylation regulates vascular endothelial growth factor receptor-2 activity</subfield>
  </datafield>
  <datafield tag="542" ind1=" " ind2=" ">
    <subfield code="l">closed</subfield>
  </datafield>
  <datafield tag="260" ind1=" " ind2=" ">
    <subfield code="c">2014-03-11</subfield>
  </datafield>
</record>