Secretion and mitogenic activity of zebrafish FGF3 reveal intermediate properties relative to mouse and Xenopus homologues.
Zebrafish (Brachyodanio rerio) Fgf-3 cDNAs expressed in COS-1 cells give rise to the heterogeneous set of secreted proteins with relative molecular masses in the range of 29-30.5 kDa. These proteins associate strongly with the extracellular matrix but are quantitatively released into the culture medium in the presence of heparin (5 micrograms/ml). Extracellular zebrafish FGF3 (ZFGF3) also contains a smaller sized component that appears to result from an amino-terminal proteolytic cleavage. These properties are similar to those described for Xenopus FGF3 (XFGF3). Receptor binding experiments indicate that ZFGF3 has a higher affinity for the IIIb rather than the IIIc isoform of FGFR2; properties that are more reminiscent of the mouse than the Xenopus homologue. Consistent with the FGF receptor binding properties, ZFGF3 shows a restricted mitogenic potential and a reduced transforming activity on NIH3T3 cells compared to XFGF3. Hybrid proteins made between Xenopus and zebrafish FGF3 implicate the C-terminal region in determining the differences in receptor potential affinities, mitogenic potency and transforming activity. Thus, ZFGF3 shows the structural and secretory properties of XFGF3, but has biological properties more akin to those of the mouse homologue.
Kiefer
P
P
Imperial Cancer Research Fund Laboratories, London, UK.
Mathieu
M
M
Mason
I
I
Dickson
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005109:Extracellular Matrix / Q000378:metabolism; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014981:Xenopus; D029867:Xenopus Proteins; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins
D017931:DNA Primers; C489198:FGF3 protein, Xenopus; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C489200:fgf3 protein, zebrafish; D005346:Fibroblast Growth Factors; D011505:Protein-Tyrosine Kinases