SECRETION AND MITOGENIC ACTIVITY OF ZEBRAFISH FGF3 REVEAL INTERMEDIATE PROPERTIES RELATIVE TO MOUSE AND XENOPUS HOMOLOGS

Zebrafish (Brachyodanio rerio) Fgf-3 cDNAs expressed in COS-1 cells gi ve rise to a heterogeneous set of secreted proteins with relative mole cular masses in the range of 29-30.5 kDa. These proteins associate str ongly with the extracellular matrix but are quantitatively released in to the culture medium in the presence of heparin (5 mu g/ml). Extracel lular zebrafish FGF3 (ZFGF3) also contains a smaller sized component t hat appears to result from an amino-terminal proteolytic cleavage. The se properties are similar to those described for Xenopus FGF3 (XFGF3). Receptor binding experiments indicate that ZFGF3 has a higher affinit y for the IIIb rather than the IIIc isoform of FGFR2; properties that are more reminiscent of the mouse than the Xenopus homologue. Consiste nt with the FGF receptor binding properties, ZFGF3 shows a restricted mitogenic potential and a reduced transforming activity on NIH3T3 cell s compared to XFGF3. Hybrid proteins made between Xenopus and zebrafis h FGF3 implicate the C-terminal region in determining the differences in receptor binding affinities, mitogenic potency and transforming act ivity. Thus, ZFGF3 shows the structural and secretory properties of XF GF3, but has biological properties more akin to those of the mouse hom ologue.