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VEGFR2 induces c-Sr...
VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd
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Sun, Zuyue (author)
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- Li, Xiujuan (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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- Massena, Sara (author)
- Uppsala universitet,Integrativ Fysiologi
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- Kutschera, Simone (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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- Padhan, Narendra (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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- Gualandi, Laura (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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Sundvold-Gjerstad, Vibeke (author)
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- Gustafsson, Karin (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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Choy, Wing Wen (author)
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- Zang, Guangxiang (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Quach, My (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Jansson, Leif (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Phillipson, Mia (author)
- Uppsala universitet,Integrativ Fysiologi
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Abid, Md Ruhul (author)
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Spurkland, Anne (author)
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- Claesson-Welsh, Lena (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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(creator_code:org_t)
- 2012-06-11
- 2012
- English.
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 209:7, s. 1363-1377
- Related links:
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http://jem.rupress.o...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Regulation of vascular endothelial (VE) growth factor (VEGF)-induced permeability is critical in physiological and pathological processes. We show that tyrosine phosphorylation of VEGF receptor 2 (VEGFR2) at Y951 facilitates binding of VEGFR2 to the Rous sarcoma (Src) homology 2-domain of T cell-specific adaptor (TSAd), which in turn regulates VEGF-induced activation of the c-Src tyrosine kinase and vascular permeability. c-Src was activated in vivo and in vitro in a VEGF/TSAd-dependent manner, and was regulated via increased phosphorylation at pY418 and reduced phosphorylation at pY527. Tsad silencing blocked VEGF-induced c-Src activation, but did not affect pathways involving phospholipase C gamma, extracellular regulated kinase, and endothelial nitric oxide. VEGF-induced rearrangement of VE-cadherin-positive junctions in endothelial cells isolated from mouse lungs, or in mouse cremaster vessels, was dependent on TSAd expression, and TSAd formed a complex with VE-cadherin, VEGFR2, and c-Src at endothelial junctions. Vessels in tsad(-/-) mice showed undisturbed flow and pressure, but impaired VEGF-induced permeability, as measured by extravasation of Evans blue, dextran, and microspheres in the skin and the trachea. Histamine-induced extravasation was not affected by TSAd deficiency. We conclude that TSAd is required for VEGF-induced, c-Src-mediated regulation of endothelial cell junctions and for vascular permeability.
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Sun, Zuyue
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Li, Xiujuan
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Massena, Sara
-
Kutschera, Simon ...
-
Padhan, Narendra
-
Gualandi, Laura
-
show more...
-
Sundvold-Gjersta ...
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Gustafsson, Kari ...
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Choy, Wing Wen
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Zang, Guangxiang
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Quach, My
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Jansson, Leif
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Phillipson, Mia
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Abid, Md Ruhul
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Spurkland, Anne
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Claesson-Welsh, ...
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show less...
- Articles in the publication
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Journal of Exper ...
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Uppsala University