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Front Cover: Molecular Basis of the Antiangiogenic Action of Rosmarinic Acid, a Natural Compound Targeting Fibroblast Growth Factor‐2/FGFR Interactions (ChemBioChem 1/2021)
Author(s) -
Pagano Katiuscia,
Carminati Laura,
Tomaselli Simona,
Molinari Henriette,
Taraboletti Giulia,
Ragona Laura
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000822
Subject(s) - fibroblast growth factor receptor , autophosphorylation , fibroblast growth factor , microbiology and biotechnology , chemistry , fibroblast growth factor receptor 1 , allosteric regulation , tyrosine kinase , phosphorylation , fgf1 , biochemistry , fibroblast growth factor receptor 2 , receptor tyrosine kinase , angiogenesis , signal transduction , biology , receptor , cancer research , protein kinase a
Less complex : Right: Fibroblast growth factor‐2 (FGF2, orange) interacts with the extracellular domain of fibroblast growth factor receptor (FGFR, red/blue) and induces the autophosphorylation of FGFR intracellular tyrosine kinase domain that, in turn, leads to complex signal transduction pathways regulating angiogenesis, tissue homeostasis, wound repair and cancer. Left: Rosmarinic acid (RA), a polyphenol present in Laminaceae family plants, binds to the extracellular domain of FGFR and induces dissociation of the FGF2/FGFR complex. NMR and docking approaches demonstrate that RA directly competes with FGF2 for the same binding site and induces allosteric perturbations further destabilizing the complex. Cellular studies show that RA binding inhibits FGF2‐induced FGFR phosphorylation, a key step in FGFR signalling. More information can be found in the full paper by K. Pagano, L. Ragona et al.