Claudin-like protein 24 interacts with the VEGFR-2 and VEGFR-3 pathways and regulates lymphatic vessel development
Identifieur interne : 002E13 ( Pmc/Curation ); précédent : 002E12; suivant : 002E14Claudin-like protein 24 interacts with the VEGFR-2 and VEGFR-3 pathways and regulates lymphatic vessel development
Auteurs : Pipsa Saharinen [Finlande] ; Hanna Helotera [Finlande] ; Juho Miettinen [Finlande] ; Camilla Norrmen [Finlande] ; Gabriela D'Amico [Finlande] ; Michael Jeltsch [Finlande] ; Tobias Langenberg [Belgique] ; Wouter Vandevelde [Belgique] ; Annelii Ny [Belgique] ; Mieke Dewerchin [Belgique] ; Peter Carmeliet [Belgique] ; Kari Alitalo [Finlande]Source :
- Genes & Development [ 0890-9369 ] ; 2010.
Abstract
The Claudin-like protein of 24 kDa (CLP24) is a hypoxia-regulated transmembrane protein of unknown function. We show here that
Url:
DOI: 10.1101/gad.565010
PubMed: 20439428
PubMed Central: 2861186
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Leuven, 3000 Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Dewerchin, Mieke" sort="Dewerchin, Mieke" uniqKey="Dewerchin M" first="Mieke" last="Dewerchin">Mieke Dewerchin</name><affiliation wicri:level="1"><nlm:aff id="aff6">Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium;</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), VIB, 3000 Leuven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Carmeliet, Peter" sort="Carmeliet, Peter" uniqKey="Carmeliet P" first="Peter" last="Carmeliet">Peter Carmeliet</name><affiliation wicri:level="1"><nlm:aff id="aff6">Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium;</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), VIB, 3000 Leuven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20439428</idno><idno type="pmc">2861186</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861186</idno><idno type="RBID">PMC:2861186</idno><idno type="doi">10.1101/gad.565010</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">002E14</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E14</idno><idno 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xml:lang="fr">Finlande</country><wicri:regionArea>Department of Virology, Haartman Institute, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation></author><author><name sortKey="Helotera, Hanna" sort="Helotera, Hanna" uniqKey="Helotera H" first="Hanna" last="Helotera">Hanna Helotera</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation></author><author><name sortKey="Miettinen, Juho" sort="Miettinen, Juho" uniqKey="Miettinen J" first="Juho" last="Miettinen">Juho Miettinen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation></author><author><name sortKey="Norrmen, Camilla" sort="Norrmen, Camilla" uniqKey="Norrmen C" first="Camilla" last="Norrmen">Camilla Norrmen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation></author><author><name sortKey="D Amico, Gabriela" sort="D Amico, Gabriela" uniqKey="D Amico G" first="Gabriela" last="D'Amico">Gabriela D'Amico</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation></author><author><name sortKey="Jeltsch, Michael" sort="Jeltsch, Michael" uniqKey="Jeltsch M" first="Michael" last="Jeltsch">Michael Jeltsch</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation></author><author><name sortKey="Langenberg, Tobias" sort="Langenberg, Tobias" uniqKey="Langenberg T" first="Tobias" last="Langenberg">Tobias Langenberg</name><affiliation wicri:level="1"><nlm:aff id="aff6">Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium;</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), VIB, 3000 Leuven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Vandevelde, Wouter" sort="Vandevelde, Wouter" uniqKey="Vandevelde W" first="Wouter" last="Vandevelde">Wouter Vandevelde</name><affiliation wicri:level="1"><nlm:aff id="aff6">Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium;</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), VIB, 3000 Leuven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Ny, Annelii" sort="Ny, Annelii" uniqKey="Ny A" first="Annelii" last="Ny">Annelii Ny</name><affiliation wicri:level="1"><nlm:aff id="aff6">Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium;</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), VIB, 3000 Leuven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Dewerchin, Mieke" sort="Dewerchin, Mieke" uniqKey="Dewerchin M" first="Mieke" last="Dewerchin">Mieke Dewerchin</name><affiliation wicri:level="1"><nlm:aff id="aff6">Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium;</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), VIB, 3000 Leuven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Carmeliet, Peter" sort="Carmeliet, Peter" uniqKey="Carmeliet P" first="Peter" last="Carmeliet">Peter Carmeliet</name><affiliation wicri:level="1"><nlm:aff id="aff6">Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium;</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), VIB, 3000 Leuven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014</wicri:regionArea></affiliation></author></analytic><series><title level="j">Genes & Development</title><idno type="ISSN">0890-9369</idno><idno type="eISSN">1549-5477</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The Claudin-like protein of 24 kDa (CLP24) is a hypoxia-regulated transmembrane protein of unknown function. We show here that <italic>clp24</italic> knockdown in <italic>Danio rerio</italic> and <italic>Xenopus laevis</italic> results in defective lymphatic development. Targeted disruption of <italic>Clp24</italic> in mice led to enlarged lymphatic vessels having an abnormal smooth muscle cell coating. We also show that the <italic>Clp24</italic><sup>−/−</sup> phenotype was further aggravated in the <italic>Vegfr2<sup>+/LacZ</sup></italic> or <italic>Vegfr3<sup>+/LacZ</sup></italic> backgrounds and that CLP24 interacts with vascular endothelial growth factor receptor-2 (VEGFR-2) and VEGFR-3 and attenuates the transcription factor CREB phosphorylation via these receptors. Our results indicate that CLP24 is a novel regulator of VEGFR-2 and VEGFR-3 signaling pathways and of normal lymphatic vessel structure.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Genes Dev</journal-id><journal-id journal-id-type="publisher-id">GAD</journal-id><journal-title-group><journal-title>Genes & Development</journal-title></journal-title-group><issn pub-type="ppub">0890-9369</issn><issn pub-type="epub">1549-5477</issn><publisher><publisher-name>Cold Spring Harbor Laboratory Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20439428</article-id><article-id pub-id-type="pmc">2861186</article-id><article-id pub-id-type="medline">8711660</article-id><article-id pub-id-type="doi">10.1101/gad.565010</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Communication</subject></subj-group></article-categories><title-group><article-title>Claudin-like protein 24 interacts with the VEGFR-2 and VEGFR-3 pathways and regulates lymphatic vessel development</article-title><alt-title alt-title-type="left-running">Saharinen et al.</alt-title><alt-title alt-title-type="right-running">CLP24, VEGFR-2, and VEGFR-3 in lymphatic development</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Saharinen</surname><given-names>Pipsa</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="author-notes" rid="fn1">8</xref></contrib><contrib contrib-type="author"><name><surname>Helotera</surname><given-names>Hanna</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="author-notes" rid="fn1">8</xref></contrib><contrib contrib-type="author"><name><surname>Miettinen</surname><given-names>Juho</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Norrmen</surname><given-names>Camilla</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>D'Amico</surname><given-names>Gabriela</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Jeltsch</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Langenberg</surname><given-names>Tobias</given-names></name><xref ref-type="aff" rid="aff6">6</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Vandevelde</surname><given-names>Wouter</given-names></name><xref ref-type="aff" rid="aff6">6</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Ny</surname><given-names>Annelii</given-names></name><xref ref-type="aff" rid="aff6">6</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Dewerchin</surname><given-names>Mieke</given-names></name><xref ref-type="aff" rid="aff6">6</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Carmeliet</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff6">6</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Alitalo</surname><given-names>Kari</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="corresp" rid="cor1">9</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Molecular/Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014, Finland;</aff><aff id="aff2"><label>2</label>Department of Virology, Haartman Institute, University of Helsinki, Helsinki FIN-00014, Finland;</aff><aff id="aff3"><label>3</label>Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014, Finland;</aff><aff id="aff4"><label>4</label>Institute for Molecular Medicine Finland, University of Helsinki, Helsinki FIN-00014, Finland;</aff><aff id="aff5"><label>5</label>Helsinki University Central Hospital, University of Helsinki, Helsinki FIN-00014, Finland;</aff><aff id="aff6"><label>6</label>Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium;</aff><aff id="aff7"><label>7</label>Vesalius Research Center (VRC), K.U. Leuven, 3000 Leuven, Belgium</aff><author-notes><fn fn-type="equal" id="fn1"><label>8</label><p>These authors contributed equally to this work.</p></fn><corresp id="cor1"><label>9</label>Corresponding author.E-MAIL <email>Kari.Alitalo@Helsinki.fi</email>; FAX 358-9-1912 5510.</corresp></author-notes><pub-date pub-type="ppub"><day>1</day><month>5</month><year>2010</year></pub-date><volume>24</volume><issue>9</issue><fpage>875</fpage><lpage>880</lpage><history><date date-type="received"><day>28</day><month>10</month><year>2009</year></date><date date-type="accepted"><day>5</day><month>3</month><year>2010</year></date></history><permissions><copyright-statement>Copyright © 2010 by Cold Spring Harbor Laboratory Press</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="875.pdf"></self-uri><abstract><p>The Claudin-like protein of 24 kDa (CLP24) is a hypoxia-regulated transmembrane protein of unknown function. We show here that <italic>clp24</italic> knockdown in <italic>Danio rerio</italic> and <italic>Xenopus laevis</italic> results in defective lymphatic development. Targeted disruption of <italic>Clp24</italic> in mice led to enlarged lymphatic vessels having an abnormal smooth muscle cell coating. We also show that the <italic>Clp24</italic><sup>−/−</sup> phenotype was further aggravated in the <italic>Vegfr2<sup>+/LacZ</sup></italic> or <italic>Vegfr3<sup>+/LacZ</sup></italic> backgrounds and that CLP24 interacts with vascular endothelial growth factor receptor-2 (VEGFR-2) and VEGFR-3 and attenuates the transcription factor CREB phosphorylation via these receptors. Our results indicate that CLP24 is a novel regulator of VEGFR-2 and VEGFR-3 signaling pathways and of normal lymphatic vessel structure.</p></abstract><kwd-group><title>Keywords:</title><kwd>CLP24</kwd><kwd>VEGFR-2</kwd><kwd>VEGFR-3</kwd><kwd>lymphangiogenesis</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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