TY  - JOUR
AU  - Savant, Soniya
AU  - La Porta, Silvia
AU  - Budnik, Annika
AU  - Busch, Katrin
AU  - Hu, Junhao
AU  - Tisch, Nathalie
AU  - Korn, Claudia
AU  - Valls, Aida Freire
AU  - Benest, Andrew V
AU  - Terhardt, Dorothee
AU  - Qu, Xianghu
AU  - Adams, Ralf H
AU  - Baldwin, H Scott
AU  - Ruiz de Almodóvar, Carmen
AU  - Rodewald, Hans-Reimer
AU  - Augustin, Hellmut
TI  - The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk Cells.
JO  - Cell reports
VL  - 12
IS  - 11
SN  - 2211-1247
CY  - Maryland Heights, MO
PB  - Cell Press
M1  - DKFZ-2017-03467
SP  - 1761 - 1773
PY  - 2015
AB  - Tie1 is a mechanistically poorly characterized endothelial cell (EC)-specific orphan receptor. Yet, Tie1 deletion is embryonic lethal and Tie1 has been implicated in critical vascular pathologies, including atherosclerosis and tumor angiogenesis. Here, we show that Tie1 does not function independently but exerts context-dependent effects on the related receptor Tie2. Tie1 was identified as an EC activation marker that is expressed during angiogenesis by a subset of angiogenic tip and remodeling stalk cells and downregulated in the adult quiescent vasculature. Functionally, Tie1 expression by angiogenic EC contributes to shaping the tip cell phenotype by negatively regulating Tie2 surface presentation. In contrast, Tie1 acts in remodeling stalk cells cooperatively to sustain Tie2 signaling. Collectively, our data support an interactive model of Tie1 and Tie2 function, in which dynamically regulated Tie1 versus Tie2 expression determines the net positive or negative effect of Tie1 on Tie2 signaling.
KW  - Receptor, TIE-1 (NLM Chemicals)
KW  - Receptor, TIE-2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26344773
DO  - DOI:10.1016/j.celrep.2015.08.024
UR  - https://inrepo02.dkfz.de/record/127444
ER  -