Brain-Derived Acidic Fibroblast Growth Factor: Complete Amino Acid Sequence and Homologies

Giménez‐Gallego, Guillermo; Rodkey, J A; Bennett, Carl D.; Rios-Candelore, Mari; DiSalvo, Jerry; Thomas, Kenneth A.

doi:10.1126/science.4071057

Cited by 326 publications

(112 citation statements)

References 22 publications

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“…The amino-terminal sequence of the protein corresponding to HPLC peak 2 was established as shown in Table2. This sequence is in agreement with the amino-terminal sequence of the previously characterized aFGF (1 -140) [5,6]. In contrast, amino-terminal sequencing of HPLC peak-1-associated protein showed a sequence identical to the amino-terminal part of fragment of the same protein, aFGF(7 -140) ( Table 2).…”

Section: Structural Characterization Of Afgfssupporting

confidence: 74%

“…Amino acid compositions of the two aFGF forms are shown in Table 1. The composition of the protein corresponding to HPLC peak 2 is very similar to that derived from the protein sequence [5,6]. The amino acid composition of HPLC peak 1 is close to that of peak 2 and, within the experimental error, compatible with the notion that peak 2 represents a truncated form of aFGF lacking the six amino-terminal residues (1 Asn, 1 Phe, 2 Leu, 1 Pro, 1 Gly, see below).…”

Section: Structural Characterization Of Afgfssupporting

confidence: 60%

“…The occurrence of two molecular forms of aFGF as described here also been suggested by others [5,291 although no details were provided. In all likelihood, they correspond to those previously observed with reverse-phase HPLC and gel electrophoresis [3, 191.…”

Section: Discussionmentioning

confidence: 95%

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Chemical and biological characterization of a truncated form of acidic fibroblast growth factor from bovine brain

Gautschi

Frater‐Schroeder

Müller

et al. 1986

European Journal of Biochemistry

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Two forms of acidic fibroblast growth factor were isolated from bovine brain by a combination of ammonium sulfate precipitation, cation-exchange chromatography, heparin-Sepharose affinity chromatography, and reversephase high-performance liquid chromatography. Amino acid analysis, polyacrylamide gel electrophoresis and amino-terminal sequence analysis showed that one form corresponds to a protein with a molecular mass of 16 kDa and the amino-terminal sequence Phe-Asn-Leu-Pro-Leu-Gly-Asn-Tyr-Lys-Lys-Pro-Lys-Leu-Leu-Tyr-and thus represents the acidic fibroblast growth factor as previously characterized EMBO J. 5, 1951 -19561. The second mitogen form has a molecular mass of 15.5 kDa. The amino-terminal sequence was established as Asn-Tyr-Lys-Lys-Pro-Lys-Leu-Leu-Tyr-. This evidence indicates that the latter form represents an amino-terminally truncated acidic fibroblast growth factor, lacking the first six amino acid residues. Both forms of the protein are biologically active and equipotent with respect to stimulation of the proliferation in vitro of mesodermal cells such as vascular endothelial and adrenal cortex cells.Two potent growth factors for mesenchymal cells, basic fibroblast growth factor (bFGF) from bovine pituitary [l, 21 and acidic fibroblast growth factor (aFGF) from bovine brain [3 -61, have recently been isolated and their amino acid sequences determined. bFGF and aFGF are structurally distinct proteins but they share extensive sequence homology [6]. Both growth factors bind to the same cellular receptors [7]. In addition to being mitogens in vitro, the two proteins possess angiogenic activity in vivo [2, 5, 81. Although no physiological role has yet been established for those mitogens, they may represent physiological angiogenesis factors thought to be involved in the regulation of neovascularization [9]. Mitogens structurally identical or very closely related to bFGF also occur in bovine [lo]

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Section: Structural Characterization Of Afgfssupporting

confidence: 74%

Section: Structural Characterization Of Afgfssupporting

confidence: 60%

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Chemical and biological characterization of a truncated form of acidic fibroblast growth factor from bovine brain

Gautschi

Frater‐Schroeder

Müller

et al. 1986

European Journal of Biochemistry

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“…The amino acid sequence deduced from the nucleotide sequence agrees well with the reported amino acid sequence of the bovine and human aFGFs. The nucleotide sequence indicates that the amino acid residue of bovine aFGF at position 45 is Gln rather than Phe as previously reported [6,30]. The open reading frame is preceded by 800 bp at the 5 '-end and is followed by untranslated region of about 3OBO bp.…”

Section: Discussionsupporting

confidence: 60%

Characterization of a bovine acidic FGF cDNA clone and its expression in brain and retina

et al. 1988

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A cDNA encoding the acidic eye-derived growth factor (EDGF II) similar to the acidic fibroblast growth factor (aFGF), a potent cell mitogen, has been isolated from a bovine retinal cDNA library. The cDNA, 4.1 kb in size, has a sequence coding for the 155 amino acids of bovine aFGF, and shows similarity with human aFGF (87% identity). The coding sequence is flanked by a 5'-untranslated region of 0.8 kb and a 3'untranslated end of 3.0 kb. Northern blot analysis of bovine brain and retina poly(A') RNAs showed the existence of four aFGF mRNA species. Two of these species are 9.9 and 6.0 kb in size, not abundant and could represent premessengers. The other two species, 4.2 and 2.5 kb, are abundant.Fibroblast growth factor; Retina; mRNA, Nucleotide sequence; (Bovine, Brain)

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“…The molecular characterization of FGF confirmed the existence of an acidic form [8] in addition to the basic one [9]; moreover, recent work has revealed the existence of a family of FGF-related proteins derived from different tumors [lo-131 and cell lines [14]. Extraordinarily high affinity for heparin is one of the important characteristics of this family.…”

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confidence: 97%

Carboxyl‐terminal structure of basic fibroblast growth factor significantly contributes to its affinity for heparin

Seno

Sasada

Kurokawa

et al. 1990

European Journal of Biochemistry

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The carboxyl-terminal sequence of basic fibroblast growth factor (bFGF) is rich in basic amino acid residues, a common characteristic amongst fibroblast growth factors, and is considered to contribute greatly to the binding to negatively charged extracellular matrixes such as heparin. To study the relationship between the affinity for heparin and the carboxyl-terminal structure of bFGF, amino-or carboxyl-terminal truncated molecules were produced in Escherichia coli using recombinant DNA techniques. These terminally truncated bFGFs were applied to a heparin-affinity HPLC column. Truncation of more than six amino acid residues from the carboxyl-terminal made the bFGF produced in E. coli markedly difficult to solubilize and weakened its affinity for heparin, though bFGF having up to 46 amino acids removed showed significant stimulation of the DNA synthesis of BALB/c3T3 cells. This stimulation of the DNA synthesis was also recognized by the bFGF having 40 amino acids removed from its amino-terminal, while the affinity of this peptide for heparin has been shown to be equal to that of the mature bFGF (146 amino acids). These results show that the affinity of bFGF for heparin depends significantly on its carboxyl-terminal structure and that the essential part for receptor binding is present between Asp4' and SerlOO. Moreover, it suggests that the Phe139Leu'40Pro141, present in all members of the FGF family, contributes greatly to the stable structure of the intact molecule. . Extraordinarily high affinity for heparin is one of the important characteristics of this family. In fact, this characteristic has been applied to the isolation and characterization of these proteins, especially basic FGF (bFGF) and acidic FGF (aFGF), from various tissues [15] and tumors [16]. The identification of specific fundamental domains of bFGF for receptor and heparin binding has been reported using synthetic polypeptides; these have suggested the existence of two domains for heparin binding and one for receptor binding [I 5 , 171. We isolated the cDNA for human bFGF and studied the expression of this cDNA in mammalian cells [18, 191 and in bacterial cells (201. We also purified and characterized the recombinant bFGF produced in Escherichia coli [20] and studied the contribution of the four cysteine residues to the protein conformation of bFGF through a site-directed mutagenesis procedure [21]. For further characterization, we constructed several bFGF molecules whose amino-or carboxyl-terminus was deleted. Here we report the structural characterization for heparin binding using these terminally truncated molecules.Correspondence to M . Seno, Biotechnology Research Laboratories, Research and Development Div., Takeda Chemical Industries Ltd, 2-17-85 Jusohonmachi, Yodogawa-ku, Osaka 532, JapanAbbreviations. F G F , fibroblast growth factor; bFGF, basic fibroblast growth factor; aFGF, acidic fibroblast growth factor.Enzymes. DNA polymerase I (EC 2.7.7.7); exonucleasc I11 (EC 3.1.11.2); lysozyme (EC 3.2.1.17); peroxidase (EC 1.11.1.7). MA...

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Brain-Derived Acidic Fibroblast Growth Factor: Complete Amino Acid Sequence and Homologies

Cited by 326 publications

References 22 publications

Chemical and biological characterization of a truncated form of acidic fibroblast growth factor from bovine brain

Chemical and biological characterization of a truncated form of acidic fibroblast growth factor from bovine brain

Characterization of a bovine acidic FGF cDNA clone and its expression in brain and retina

Carboxyl‐terminal structure of basic fibroblast growth factor significantly contributes to its affinity for heparin

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