Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-16610-z
Keywords
-
Categories
Funding
- American Heart Association [16SDG26940002]
- American Cancer Society, Illinois Division [282802]
- National Science Foundation (NSF) [1743333, 1743334, 1640783]
- National Science Foundation (NSF CAREER) [1653925]
- National Science Foundation (NSF CBET) [1512598]
- National Science Foundation (NSF BPE) [1648454]
- National Science Foundation
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1653925, 1512598] Funding Source: National Science Foundation
- Directorate For Engineering
- Div Of Engineering Education and Centers [1648454] Funding Source: National Science Foundation
Ask authors/readers for more resources
Nearly all studies of angiogenesis have focused on uni-family ligand-receptor binding, e.g., VEGFs bind to VEGF receptors, PDGFs bind to PDGF receptors, etc. The discovery of VEGF-PDGFRs binding challenges this paradigm and calls for investigation of other ligand-receptor binding possibilities. We utilized surface plasmon resonance to identify and measure PDGF-to-VEGFR binding rates, establishing cut-offs for binding and non-binding interactions. We quantified the kinetics of the recent VEGF-A:PDGFR beta interaction for the first time with K-D = 340 pM. We discovered new PDGF:VEGFR2 interactions with PDGF-AA:R2 K-D = 530 nM, PDGF-AB:R2 K-D = 110 pM, PDGF-BB:R2 K-D = 40 nM, and PDGF-CC:R2 K-D = 70 pM. We computationally predict that cross-family PDGF binding could contribute up to 96% of VEGFR2 ligation in healthy conditions and in cancer. Together the identification, quantification, and simulation of these novel cross-family interactions posits new mechanisms for understanding anti-angiogenic drug resistance and presents an expanded role of growth factor signaling with significance in health and disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available