VEGF receptor 2/‐3 heterodimers detected in situ by proximity ligation on angiogenic sprouts
Identifieur interne : 005B47 ( Main/Exploration ); précédent : 005B46; suivant : 005B48VEGF receptor 2/‐3 heterodimers detected in situ by proximity ligation on angiogenic sprouts
Auteurs : Ingrid Nilsson [Suède] ; Fuad Bahram [Suède] ; Xiujuan Li [Suède] ; Laura Gualandi [Suède] ; Sina Koch [Suède] ; Malin Jarvius [Suède] ; Ola Söderberg [Suède] ; Andrey Anisimov [Finlande] ; Ivana Kholová [Finlande] ; Bronislaw Pytowski [États-Unis] ; Megan Baldwin [Australie] ; Seppo Yl Erttuala [Finlande] ; Kari Alitalo [Finlande] ; Johan Kreuger [Suède] ; Lena Claesson-Welsh [Suède]Source :
- The EMBO Journal [ 0261-4189 ] ; 2010-04-21.
Abstract
The vascular endothelial growth factors VEGFA and VEGFC are crucial regulators of vascular development. They exert their effects by dimerization and activation of the cognate receptors VEGFR2 and VEGFR3. Here, we have used in situ proximity ligation to detect receptor complexes in intact endothelial cells. We show that both VEGFA and VEGFC potently induce formation of VEGFR2/‐3 heterodimers. Receptor heterodimers were found in both developing blood vessels and immature lymphatic structures in embryoid bodies. We present evidence that heterodimers frequently localize to tip cell filopodia. Interestingly, in the presence of VEGFC, heterodimers were enriched in the leading tip cells as compared with trailing stalk cells of growing sprouts. Neutralization of VEGFR3 to prevent heterodimer formation in response to VEGFA decreased the extent of angiogenic sprouting. We conclude that VEGFR2/‐3 heterodimers on angiogenic sprouts induced by VEGFA or VEGFC may serve to positively regulate angiogenic sprouting.
Url:
- https://api.istex.fr/document/EDDD5C02372DAE6BA2D451FE5EA9CA6FED41AF2D/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868571
DOI: 10.1038/emboj.2010.30
Affiliations:
- Australie, Finlande, Suède, États-Unis
- East Middle Sweden, Svealand, Uusimaa, État de New York
- Helsinki, Uppsala
- Université d'Helsinki, Université d'Uppsala
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last="Kholová">Ivana Kholová</name><affiliation wicri:level="1"><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio</wicri:regionArea><wicri:noRegion>Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Pytowski, Bronislaw" sort="Pytowski, Bronislaw" uniqKey="Pytowski B" first="Bronislaw" last="Pytowski">Bronislaw Pytowski</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Imclone Systems Corporation, NY, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Baldwin, Megan" sort="Baldwin, Megan" uniqKey="Baldwin M" first="Megan" last="Baldwin">Megan Baldwin</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Vegenics Limited, Toorak, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Yl Erttuala, Seppo" sort="Yl Erttuala, Seppo" uniqKey="Yl Erttuala S" first="Seppo" last="Yl Erttuala">Seppo Yl Erttuala</name><affiliation wicri:level="1"><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio</wicri:regionArea><wicri:noRegion>Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation wicri:level="4"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular and Cancer Biology Research Program, University of Helsinki, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author><author><name sortKey="Kreuger, Johan" sort="Kreuger, Johan" uniqKey="Kreuger J" first="Johan" last="Kreuger">Johan Kreuger</name><affiliation wicri:level="4"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Claesson Elsh, Lena" sort="Claesson Elsh, Lena" uniqKey="Claesson Elsh L" first="Lena" last="Claesson-Welsh">Lena Claesson-Welsh</name><affiliation wicri:level="4"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Suède</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The EMBO Journal</title><title level="j" type="alt">THE EMBO JOURNAL</title><idno type="ISSN">0261-4189</idno><idno type="eISSN">1460-2075</idno><imprint><biblScope unit="vol">29</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1377">1377</biblScope><biblScope unit="page" to="1388">1388</biblScope><biblScope unit="page-count">12</biblScope><publisher>John Wiley & Sons, Ltd</publisher><pubPlace>Chichester, UK</pubPlace><date type="published" when="2010-04-21">2010-04-21</date></imprint><idno type="ISSN">0261-4189</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0261-4189</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">The vascular endothelial growth factors VEGFA and VEGFC are crucial regulators of vascular development. They exert their effects by dimerization and activation of the cognate receptors VEGFR2 and VEGFR3. Here, we have used in situ proximity ligation to detect receptor complexes in intact endothelial cells. We show that both VEGFA and VEGFC potently induce formation of VEGFR2/‐3 heterodimers. Receptor heterodimers were found in both developing blood vessels and immature lymphatic structures in embryoid bodies. We present evidence that heterodimers frequently localize to tip cell filopodia. Interestingly, in the presence of VEGFC, heterodimers were enriched in the leading tip cells as compared with trailing stalk cells of growing sprouts. Neutralization of VEGFR3 to prevent heterodimer formation in response to VEGFA decreased the extent of angiogenic sprouting. We conclude that VEGFR2/‐3 heterodimers on angiogenic sprouts induced by VEGFA or VEGFC may serve to positively regulate angiogenic sprouting.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Finlande</li><li>Suède</li><li>États-Unis</li></country><region><li>East Middle Sweden</li><li>Svealand</li><li>Uusimaa</li><li>État de New York</li></region><settlement><li>Helsinki</li><li>Uppsala</li></settlement><orgName><li>Université d'Helsinki</li><li>Université d'Uppsala</li></orgName></list><tree><country name="Suède"><region name="Svealand"><name sortKey="Nilsson, Ingrid" sort="Nilsson, Ingrid" uniqKey="Nilsson I" first="Ingrid" last="Nilsson">Ingrid Nilsson</name></region><name sortKey="Bahram, Fuad" sort="Bahram, Fuad" uniqKey="Bahram F" first="Fuad" last="Bahram">Fuad Bahram</name><name sortKey="Claesson Elsh, Lena" sort="Claesson Elsh, Lena" uniqKey="Claesson Elsh L" first="Lena" last="Claesson-Welsh">Lena Claesson-Welsh</name><name sortKey="Claesson Elsh, Lena" sort="Claesson Elsh, Lena" uniqKey="Claesson Elsh L" first="Lena" last="Claesson-Welsh">Lena Claesson-Welsh</name><name sortKey="Gualandi, Laura" sort="Gualandi, Laura" uniqKey="Gualandi L" first="Laura" last="Gualandi">Laura Gualandi</name><name sortKey="Jarvius, Malin" sort="Jarvius, Malin" uniqKey="Jarvius M" first="Malin" last="Jarvius">Malin Jarvius</name><name sortKey="Koch, Sina" sort="Koch, Sina" uniqKey="Koch S" first="Sina" last="Koch">Sina Koch</name><name sortKey="Kreuger, Johan" sort="Kreuger, Johan" uniqKey="Kreuger J" first="Johan" last="Kreuger">Johan Kreuger</name><name sortKey="Li, Xiujuan" sort="Li, Xiujuan" uniqKey="Li X" first="Xiujuan" last="Li">Xiujuan Li</name><name sortKey="Soderberg, Ola" sort="Soderberg, Ola" uniqKey="Soderberg O" first="Ola" last="Söderberg">Ola Söderberg</name></country><country name="Finlande"><region name="Uusimaa"><name sortKey="Anisimov, Andrey" sort="Anisimov, Andrey" uniqKey="Anisimov A" first="Andrey" last="Anisimov">Andrey Anisimov</name></region><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Kholova, Ivana" sort="Kholova, Ivana" uniqKey="Kholova I" first="Ivana" last="Kholová">Ivana Kholová</name><name sortKey="Yl Erttuala, Seppo" sort="Yl Erttuala, Seppo" uniqKey="Yl Erttuala S" first="Seppo" last="Yl Erttuala">Seppo Yl Erttuala</name></country><country name="États-Unis"><region name="État de New York"><name sortKey="Pytowski, Bronislaw" sort="Pytowski, Bronislaw" uniqKey="Pytowski B" first="Bronislaw" last="Pytowski">Bronislaw Pytowski</name></region></country><country name="Australie"><noRegion><name sortKey="Baldwin, Megan" sort="Baldwin, Megan" uniqKey="Baldwin M" first="Megan" last="Baldwin">Megan Baldwin</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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