FGF1 and FGF2 Induced FGFR3 Dimerization in Plasma Membrane Derived Vesicles

Abstract

Fibroblast growth factor receptor 3 (FGFR3) is a receptor tyrosine kinase which resides in the plasma membrane and regulates cell survival, differentiation and angiogenesis. Fibroblast growth factors (fgfs) are a family of secreted protein ligands which bind to FGFRs to potentiate signaling. FGFR3 functions via lateral dimerization in the cellular plasma membrane. It has been shown that FGFR3 forms dimers in the absence of fgf ligands, however it is not clear how fgfs affect FGFR3 dimerization. Previously we have developed a quantitative imaging FRET (QI-FRET) technique to study membrane protein interactions in a cell-derived model system. Here we have used this method to measure thermodynamics of FGFR3 interactions in the presence of fgf1 and fgf2 in Chinese Hamster Ovary (CHO) cell derived vesicles. These measurements provide novel mechanistic insights into the role of ligand binding in receptor tyrosine kinase interactions.