PROCESSING, SECRETION, AND BIOLOGICAL PROPERTIES OF A NOVEL GROWTH-FACTOR OF THE FIBROBLAST GROWTH-FACTOR FAMILY WITH ONCOGENIC POTENTIAL
PROCESSING, SECRETION, AND BIOLOGICAL PROPERTIES OF A NOVEL GROWTH-FACTOR OF THE FIBROBLAST GROWTH-FACTOR FAMILY WITH ONCOGENIC POTENTIAL
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DOI：
10.1128/mcb.8.7.2933
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发表时间：
1988-07-01
影响因子：
5.3
通讯作者：
BASILICO, C
中科院分区：
文献类型：
--
作者：
DELLIBOVI, P;CURATOLA, AM;BASILICO, C
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-fdf 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 indistinguisable in its molecular weight, glycosylation, secretion, and biologial 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.
