Vztah struktury a funkce v signálováni fibroblastových růstových faktorů
Fibroblast growth factors (FGFs) interact with four types of cell surface receptors (FGFRs) to deliver signals critical for development and functioning of mammalian organs. FGFs trigger proliferative, migrational, anti-apoptotic and metabolic signaling, representing an attractive therapeutic option for tissue regeneration, metabolic syndromes and aging. Such use is however complicated by our poor knowledge of the molecular basis of FGF signaling. How a particular FGF regulates diverse cell responses is not known, and is the subject of the proposal. We will study the structure-function relationship of FGFs by engineering four members of FGF family, FGF8, FGF9, FGF10 and FGF18. We will obtain mutants with increased thermal stability and modified ability to interact with FGFRs and heparan sulphate. These FGF variants will be tested in cells for their ability to activate different types of signaling. The proposed research will unravel structural and biophysical properties of FGFs, which drive the specific cell response.