% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Fearnley:119924,
author = {G. W. Fearnley and A. F. Odell and A. M. Latham and N. A.
Mughal and A. F. Bruns and N. J. Burgoyne and S.
Homer-Vanniasinkam and I. C. Zachary and M. Hollstein$^*$
and S. B. Wheatcroft and S. Ponnambalam},
title = {{VEGF}-{A} isoforms differentially regulate
{ATF}-2-dependent {VCAM}-1 gene expression and
endothelial-leukocyte interactions.},
journal = {Molecular biology of the cell},
volume = {25},
number = {16},
issn = {1059-1524},
address = {Bethesda, Md.},
publisher = {American Society for Cell Biology},
reportid = {DKFZ-2017-00515},
pages = {2509 - 2521},
year = {2014},
abstract = {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.},
keywords = {ATF2 protein, human (NLM Chemicals) / Activating
Transcription Factor 2 (NLM Chemicals) / Protein Isoforms
(NLM Chemicals) / VEGFA protein, human (NLM Chemicals) /
Vascular Cell Adhesion Molecule-1 (NLM Chemicals) / Vascular
Endothelial Growth Factor A (NLM Chemicals) / KDR protein,
human (NLM Chemicals) / Vascular Endothelial Growth Factor
Receptor-2 (NLM Chemicals)},
cin = {C016},
ddc = {570},
cid = {I:(DE-He78)C016-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24966171},
pmc = {pmc:PMC4142621},
doi = {10.1091/mbc.E14-05-0962},
url = {https://inrepo02.dkfz.de/record/119924},
}