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Transcriptional pro...
Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis.
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- Mellberg, Sofie (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Dimberg, Anna (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Bahram, Fuad (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Hayashi, Makoto (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Rennel, Emma (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Ameur, Adam (author)
- Uppsala universitet,Centrum för bioinformatik
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- Westholm, Jakub Orzechowski (author)
- Uppsala universitet,Centrum för bioinformatik
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- Larsson, Erik, 1975 (author)
- Uppsala universitet,Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory,Institutionen för immunologi, genetik och patologi
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- Lindahl, Per, 1967 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Cross, Michael J (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Claesson-Welsh, Lena (author)
- Uppsala universitet,Institutionen för genetik och patologi
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(creator_code:org_t)
- 2009-01-09
- 2009
- English.
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In: The FASEB journal. - : Wiley. - 1530-6860 .- 0892-6638. ; 23:5, s. 1490-1502
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https://doi.org/10.1...
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Abstract
Subject headings
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- To define molecular events accompanying formation of the 3-dimensional (3D) vascular tube, we have characterized gene expression during vascular endothelial growth factor (VEGF)-induced tubular morphogenesis of endothelial cells. Microarray analyses were performed comparing gene induction in growth-arrested, tube-forming endothelial cells harvested from 3D collagen cultures to that in proliferating endothelial cells cultured on fibronectin. Differentially expressed genes were clustered and analyzed for specific endothelial expression through publicly available datasets. We validated the contribution of one of the identified genes, vascular endothelial protein tyrosine phosphatase (VE-PTP), to endothelial morphogenesis. Silencing of VE-PTP expression was accompanied by increased VEGF receptor-2 (VEGFR2) tyrosine phosphorylation and activation of downstream signaling pathways. The increased VEGFR2 activity promoted endothelial cell cycle progression, overcoming the G(0)/G(1) arrest associated with organization into tubular structures in the 3D cultures. Proximity ligation showed close association between VEGFR2 and VE-PTP in resting cells. Activation of VEGFR2 by VEGF led to rapid loss of association, which was resumed with time in parallel with decreased receptor activity. In conclusion, we have identified genes, which may serve critical functions in formation of the vascular tube. One of these, VE-PTP, regulates VEGFR2 activity thereby modulating the VEGF-response during angiogenesis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Cells
- Cultured
- Endothelial Cells
- ultrastructure
- Gene Expression Profiling
- Gene Expression Regulation
- Developmental
- Humans
- Morphogenesis
- genetics
- Receptor-Like Protein Tyrosine Phosphatases
- Class 3
- physiology
- Signal Transduction
- Vascular Endothelial Growth Factor Receptor-2
- physiology
- angiogenesis
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Mellberg, Sofie
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Dimberg, Anna
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Bahram, Fuad
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Hayashi, Makoto
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Rennel, Emma
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Ameur, Adam
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Westholm, Jakub ...
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Larsson, Erik, 1 ...
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Lindahl, Per, 19 ...
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Cross, Michael J
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Claesson-Welsh, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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The FASEB journa ...
- By the university
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University of Gothenburg
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Uppsala University