Processing, secretion, and biological properties of a novel growth factor of the fibroblast growth factor family with oncogenic potential - PubMed (original) (raw)
Processing, secretion, and biological properties of a novel growth factor of the fibroblast growth factor family with oncogenic potential
P Delli-Bovi et al. Mol Cell Biol. 1988 Jul.
Abstract
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.
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References
- J Cell Biol. 1982 Jan;92(1):1-22 - PubMed
- J Biol Chem. 1981 Aug 10;256(15):7990-7 - PubMed
- Mol Cell Biol. 1982 Feb;2(2):161-70 - PubMed
- J Cell Biol. 1982 Dec;95(3):974-81 - PubMed
- Nucleic Acids Res. 1983 Mar 11;11(5):1295-308 - PubMed
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