Mattias Belting1, 7, Michael I Dorrell2, 7, Staffan Sandgren3, Edith Aguilar2, Jasimuddin Ahamed1, Andrea Dorfleutner1, 6, Peter Carmeliet4, Barbara M Mueller5, Martin Friedlander2
& Wolfram Ruf11
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
2
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
3
Biomedical Centre, C-13, Lund University, SE-221 84 Lund, Sweden.
4
Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium, B-3000.
5
Division of Cancer Biology, La Jolla Institute for Molecular Medicine, 4570 Executive Drive, San Diego, California 92121, USA.
6
Present address: The Mary Babb Randolph Cancer Center and the Department of Microbiology and Immunology, West Virginia University, Morgantown, West Virginia 26506, USA.
7
These authors contributed equally to this work.
Correspondence should be addressed to Martin Friedlander friedlan@scripps.edu or Wolfram Ruf ruf@scripps.edu
CT mice) show enhanced PAR-2-dependent angiogenesis, in synergy with platelet-derived growth factor BB (PDGF-BB). Ocular tissue from diabetic patients shows PAR-2 colocalization with phosphorylated TF specifically on neovasculature, suggesting that phosphorylation of the TF cytoplasmic domain releases its negative regulatory control of PAR-2 signaling in angiogenesis. Targeting the TF-VIIa signaling pathway may thus enhance the efficacy of angiostatic treatments for cancer and neovascular eye diseases.
