Dissecting biological activities of fibroblast growth factor receptors by the coiled-coil-mediated oligomerization of FGF1.

摘要: Abstract Fibroblast growth factor receptors (FGFRs) are integral membrane proteins involved in various biological processes including proliferation, migration and apoptosis. There a number of regulatory mechanisms FGFR signaling, which tightly control the specificity duration transmitted signals. The effect FGFRs spatial distribution plasma on receptor-dependent functions is still largely unknown. We have demonstrated that oligomerization FGF1 with coiled-coil motifs improves affinity for heparin. Set developed oligomers evoked prolonged activation FGFR1 receptor-downstream signaling pathways, as compared to wild type FGF1. majority obtained oligomeric variants showed increased stability, enhanced mitogenic activity improved internalization via FGFR1-dependent endocytosis. Importantly, highest state exhibited reduced ability stimulate FGFR-dependent glucose uptake, while at same time remained hyperactive induction cell proliferation. Our data implicate alters FGF/GFR1 system. Furthermore, oligomers, due stability proliferative potential, can be applied regenerative medicine or drug delivery vehicles ADC approach against FGFR1-overproducing cancers.