Human basic fibroblast growth factor: nucleotide sequence and genomic organization.

Abstract

Clones encoding the angiogenic endothelial cell mitogen, basic fibroblast growth factor (FGF), have been isolated from human cDNA libraries made from kidney, fetal heart, fetal liver, term placenta, and a breast carcinoma. Basic FGF cDNA clones are present in these libraries at very low levels when compared to the quantity of the growth factor in the tissues. This observation, combined with the fact that several of the clones represent unspliced transcripts, suggests that cytoplasmic basic FGF mRNA is unstable and that the protein is stored in tissues. The amino acid sequence of human basic FGF, deduced from the sequence of these cDNAs and from genomic clones, is 99% homologous to that of bovine basic FGF, implying a strong selection pressure for maintenance of function and structure. As with the bovine factor, human basic FGF does not appear to have a signal peptide sequence. Southern blot analysis of human genomic DNA and mapping of the cloned gene shows that there is only one basic FGF gene. All of the basic, heparin‐binding endothelial cell mitogens of similar amino acid composition that have been described must therefore be products of this single gene.

Antibodies against basic fibroblast growth factor inhibit the autocrine growth of pulmonary artery endothelial cells

“…bFGF has no typical signal sequence [18,19] suggesting that it may be transported to the outside of the cell via a different pathway from that of normal secretory proteins. The transport and secretion mechanisms are to be elucidated.…”

Expressions of Basic Fibroblast Growth Factor and Its Receptors and Their Relationship to Proliferation of Human Hepatocellular Carcinoma Cell Lines

“…44 However, among the FGF family, bFGF and acidic FGF genes do not encode conventional signal peptide sequences for extracellular FGF release. 3,4,11,22 Consequently, mous cell proliferation mechanisms, such as autocrine, mediated by bFGF/FGFR, at least, in the five cell lines.…”

“…At pres-cytoplasm of hepatocellular carcinoma (HCC) cells of 16 of ent, nine members, from FGF-1 to FGF-9, have been identi-56 patients (29%), and another study reported the cultured fied. [1][2][3][4][5][6][7][8][9] The FGF family has been widely distributed in normal HCC cell line, SK Hep-1, can produce bFGF in vitro. 31 Normal and/or tumor tissues, and they are known to take various hepatocytes do not express the bFGF receptor, FGFR-1, while important roles, e.g., in angiogenesis, tissue regeneration, a hepatoblastoma cell line (HepG2) has been reported to exwound healing, and embryonic development.…”

Both FGF1 and Bcl-x synthesis are necessary for the reduction of apoptosis in retinal pigmented epithelial cells by FGF2: role of the extracellular signal-regulated kinase 2

“…FGF1 and 2 have been implicated in tumor development and malignant progression (for review see Rifkin and Moscatelli, 1989;Courlier et al, 1997). FGF1 and 2 lack a classic signal peptide (Abraham et al, 1986;Jaye et al, 1986), implying that they are not secreted by the classical secretion pathway. There is evidence that FGF1 and 2 are exported from the cell and subsequently act as autocrine or paracrine factors (Vlodavski et al, 1982;Sato and Rifkin, 1988).…”