001     119924
005     20240228135001.0
024 7 _ |a 10.1091/mbc.E14-05-0962
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024 7 _ |a pmc:PMC4142621
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024 7 _ |a 1044-2030
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024 7 _ |a 1059-1524
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024 7 _ |a 1939-4586
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037 _ _ |a DKFZ-2017-00515
041 _ _ |a eng
082 _ _ |a 570
100 1 _ |a Fearnley, Gareth W
|b 0
245 _ _ |a VEGF-A isoforms differentially regulate ATF-2-dependent VCAM-1 gene expression and endothelial-leukocyte interactions.
260 _ _ |a Bethesda, Md.
|c 2014
|b American Society for Cell Biology
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular physiology. VEGF-A stimulates signal transduction pathways that modulate endothelial outputs such as cell migration, proliferation, tubulogenesis, and cell-cell interactions. Multiple VEGF-A isoforms exist, but the biological significance of this is unclear. Here we analyzed VEGF-A isoform-specific stimulation of VCAM-1 gene expression, which controls endothelial-leukocyte interactions, and show that this is dependent on both ERK1/2 and activating transcription factor-2 (ATF-2). VEGF-A isoforms showed differential ERK1/2 and p38 MAPK phosphorylation kinetics. A key feature of VEGF-A isoform-specific ERK1/2 activation and nuclear translocation was increased phosphorylation of ATF-2 on threonine residue 71 (T71). Using reverse genetics, we showed ATF-2 to be functionally required for VEGF-A-stimulated endothelial VCAM-1 gene expression. ATF-2 knockdown blocked VEGF-A-stimulated VCAM-1 expression and endothelial-leukocyte interactions. ATF-2 was also required for other endothelial cell outputs, such as cell migration and tubulogenesis. In contrast, VCAM-1 was essential only for promoting endothelial-leukocyte interactions. This work presents a new paradigm for understanding how soluble growth factor isoforms program complex cellular outputs and responses by modulating signal transduction pathways.
536 _ _ |a 313 - Cancer risk factors and prevention (POF3-313)
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650 _ 7 |a ATF2 protein, human
|2 NLM Chemicals
650 _ 7 |a Activating Transcription Factor 2
|2 NLM Chemicals
650 _ 7 |a Protein Isoforms
|2 NLM Chemicals
650 _ 7 |a VEGFA protein, human
|2 NLM Chemicals
650 _ 7 |a Vascular Cell Adhesion Molecule-1
|2 NLM Chemicals
650 _ 7 |a Vascular Endothelial Growth Factor A
|2 NLM Chemicals
650 _ 7 |a KDR protein, human
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a Vascular Endothelial Growth Factor Receptor-2
|0 EC 2.7.10.1
|2 NLM Chemicals
700 1 _ |a Odell, Adam F
|b 1
700 1 _ |a Latham, Antony M
|b 2
700 1 _ |a Mughal, Nadeem A
|b 3
700 1 _ |a Bruns, Alexander F
|b 4
700 1 _ |a Burgoyne, Nicholas J
|b 5
700 1 _ |a Homer-Vanniasinkam, Shervanthi
|b 6
700 1 _ |a Zachary, Ian C
|b 7
700 1 _ |a Hollstein, Monica
|0 P:(DE-He78)f3bec70c95e9e3dce0f39d54b3843118
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|u dkfz
700 1 _ |a Wheatcroft, Stephen B
|b 9
700 1 _ |a Ponnambalam, Sreenivasan
|b 10
773 _ _ |a 10.1091/mbc.E14-05-0962
|g Vol. 25, no. 16, p. 2509 - 2521
|0 PERI:(DE-600)1474922-1
|n 16
|p 2509 - 2521
|t Molecular biology of the cell
|v 25
|y 2014
|x 1059-1524
909 C O |o oai:inrepo02.dkfz.de:119924
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910 1 _ |a Deutsches Krebsforschungszentrum
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914 1 _ |y 2014
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