Processing, secretion, and biological properties of a novel growth factor of the fibroblast growth factor family with oncogenic potential.
We recently reported that the protein encoded in a novel human oncogene isolated from Kaposi sarcoma DNA was a growth factor with significant homology to basic and acidic fibroblast growth factors (FGFs). To study the properties of this growth factor (referred to as K-FGF) and the mechanism by which the K-fgf oncogene transforms cells, we have studied the production and processing of K-FGF in COS-1 cells transfected with a plasmid encoding the K-fgf cDNA. The results show that, unlike basic and acidic FGFs, the K-FGF protein is cleaved after a signal peptide, glycosylated, and efficiently secreted as a mature protein of 176 or 175 amino acids. Inhibition of glycosylation impaired secretion, and the stability of the secreted K-FGF was greatly enhanced by the presence of heparin in the cultured medium. We have used the conditioned medium from transfected COS-1 cells to test K-FGF biological activity. Similar to basic FGF, the K-FGF protein was mitogenic for fibroblasts and endothelial cells and induced the growth of NIH 3T3 mouse cells in serum-free medium. Accordingly, K-fgf-transformed NIH 3T3 cells grew in serum-free medium, consistent with an autocrine mechanism of growth. We have also expressed the protein encoded in the K-fgf protooncogene in COS-1 cells, and it was indistinguishable in its molecular weight, glycosylation, secretion, and biological activity from K-FGF. Taken together, these results suggest that the mechanism of activation of this oncogene is due to overexpression rather than to mutations in the coding sequences.
D000818:Animals; D002455:Cell Division; D002461:Cell Line, Transformed; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006493:Heparin / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D009857:Oncogenes; D012514:Sarcoma, Kaposi / Q000032:analysis*; D014162:Transfection
D005346:Fibroblast Growth Factors; D006493:Heparin; D004247:DNA