title: The physical basis of FGFR3 response to fgf1 and fgf2.
abstract: Fibroblast growth factors (fgfs) play important roles in embryonic development and in adult life by controlling cell proliferation, differentiation, and migration. There are 18 known fgfs which activate four fibroblast growth factor receptors (FGFRs), with different isoforms due to alternative splicing. The physical basis behind the specificity of the biological responses mediated by different fgf-FGFR pairs is currently unknown. To gain insight into the specificity of FGFR3c, a membrane receptor which is critical for bone development, we studied, analyzed, and compared the activation of FGFR3c over a wide range of fgf1 and fgf2 concentrations. We found that while the strength of fgf2 binding to FGFR3c is lower than the strength of fgf1 binding, the fgf2-bound dimers exhibit higher phosphorylation of the critical tyrosines in the activation loop. As a result, fgf1 and fgf2 elicit a similar FGFR3c response at low, but not at high, concentrations. The results demonstrate the versatility of FGFR3c response to fgf1 and fgf2 and highlight the complexity in fgf signaling.
authors: Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
authors: Fenghao
authors: F
authors: Chen
authors: Kalina
authors: K
authors: Hristova
mesh_terms: D002460:Cell Line; D019281:Dimerization; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010766:Phosphorylation; D011485:Protein Binding; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D051498:Receptor, Fibroblast Growth Factor, Type 3