A series of peptides, termed dekafins, were derived from the beta10-beta11 loop regions of fibroblast growth factors (FGFs) 1, 2, 3, 5, 6, 8, 9, 10, and 17. The dekafins share a homologous amino acid sequence similar to a sequence in the first fibronectin type III module of the neural cell adhesion molecule. All dekafins were shown by surface plasmon resonance analysis to bind fibroblast growth factor receptor (FGFR)1-IIIc-Ig2-3 and FGFR2-IIIb-Ig2-3, respectively, with K(d) values of approximately 10(-7) to 10(-8) mol/L. Binding of dekafin1 to FGFR1-IIIc-Ig2-3 was inhibited by a heparin analog, sucrose octasulfate, indicating that heparin sulfate moiety can modulate dekafin binding to FGFRs. Treatment of transcription and mRNA export (TREX) cells permanently expressing Strep-tag-labeled FGFR1-IIIc with dekafins resulted in receptor phosphorylation. FGF1-induced FGFR1-IIIc phosphorylation was inhibited by dekafin1 and 10 in high concentrations, indicating that dekafins are FGFR partial agonists. The dekafins induced neuronal differentiation as reflected by neurite outgrowth from cerebellar granule neurons, an effect that was abolished by SU5402, a specific inhibitor of the FGFR tyrosine kinase, and by inositolhexaphosphate, an extracellularly acting FGFR antagonist. Some, but not all, dekafins were capable of promoting survival of cerebellar granule neurons induced to undergo apoptosis. Thus, the dekafins are functional FGFR agonists with apparent therapeutic potential.