Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basic fibroblast growth factor (bFGF) is a potent endothelial cell mitogen whose actions are mediated by binding to specific cell surface receptors on a variety of cell types. However, the amino acid sequence of bFGF does not contain a classical signal peptide sequence and the extent to which cellular stores of this mitogen are released is still a matter of some controversy. In the present study we examined the release of immunoreactive bFGF into serum-free conditioned medium of bovine corneal endothelial cells (BCE) and a human astrocytoma cell line, U87-MG. Western blotting analysis of BCE conditioned medium using N-terminal specific anti-bFGF serum revealed a single immunoreactive band of 32 kilodaltons, which was reduced to 18 kilodaltons in the presence of 8 M urea. Using a sensitive two-site immunoradiometric assay we were able to quantify the release of immunoreactive bFGF into the culture medium by BCE cells and by the human astrocytoma cell line U87-MG. In each case the release of bFGF was cell density dependent, but under all conditions the level of bFGF released was significantly greater in the transformed astrocytoma line, ranging from 15- to 50-fold higher than in the BCE cultures under various conditions. At 30% confluence the concentration of immunoreactive bFGF in the medium was maintained at a constant level for up to 24 h. However, the level of immunoreactive bFGF declined rapidly in confluent cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Apr
PMID:Fibroblast growth factor release by bovine endothelial cells and human astrocytoma cells in culture is density dependent. 272 35

We previously described the isolation of a human oncogene which had acquired transforming potential by a DNA rearrangement accompanying transfection of NIH 3T3 cells with human tumor DNA (X. Zhan, A. Culpepper, M. Reddy, J. Loveless, and M. Goldfarb, Oncogene 1:369-376, 1987). We now term this oncogene the FGF-5 gene, since it specifies the fifth documented protein related to fibroblast growth factors (FGFs. Two regions of the FGF-5 sequence, containing 122 of its 267 amino acid residues, were 40 to 50% homologous to the sequences of acidic and basic FGFs as well as to the sequences of the FGF-related oncoproteins int-2 and hst/KS3. The FGF-5 gene bears the three exon structures typical for members of this family. FGF-5 was found to be expressed in the neonatal brain and in 3 of the 13 human tumor cell lines examined. Several experiments strongly suggested that FGF-5 is a growth factor with properties common to those of acidic and basic FGFs. The rearrangement which activated the FGF-5 gene during DNA transfection had juxtaposed a retrovirus transcriptional enhancer just upstream from the native promoter of the gene.
Mol Cell Biol 1988 Aug
PMID:The human FGF-5 oncogene encodes a novel protein related to fibroblast growth factors. 321 Nov 47

The relationship between growth factor responses and androgen-induced cell proliferation was studied in a mouse renal tumor (RAG) cell line, a hybrid (F614B16) rat prostate x RAG cell line, and an 8-azaguanine-resistant revertant of the F614B16 cell line. The hybrid F614B16 cells are very sensitive to androgens; treatment with 20 nM 5 alpha-dihydrotestosterone accelerated cell growth in the presence or absence of serum. In contrast, the RAG cells and 8-azaguanine-resistant F614B16 cells responded to 5 alpha-dihydrotestosterone only in the absence of serum. Variation in the proliferative response to androgens among these cell lines was associated with variation in growth factor sensitivity. Basic fibroblast growth factor (bFGF) stimulated basal and androgen-induced growth of F614B16 cells in serum-free and serum-supplemented media, whereas it inhibited RAG cell growth. Basic FGF stimulated basal, but not androgen-induced growth of revertant F614B16 cells. The cell lines also differed in sensitivity to epidermal growth factor, which had no effect on hybrid cell growth but inhibited RAG and revertant cell growth in a dose-dependent fashion in serum-free media. The results of these studies suggest that androgen-sensitivity is associated with a positive response to FGF and insensitivity to exogenous epidermal growth factor.
Mol Endocrinol 1988 Apr
PMID:Relationship between androgen-induced cell proliferation and sensitivity to exogenous growth factors. 326 5

Induction of quiescent BALB/c 3T3 murine fibroblasts by platelet-derived growth factor (PDGF) or fibroblast growth factor (FGFs) is accompanied by induction of c-myc gene expression. To study the role of c-myc in cell growth, we transfected BALB/c 3T3 cells with a plasmid construct containing a glucocorticoid-inducible c-myc gene. When these transfected cells were growth arrested in PDGF-FGF-freedefined medium, glucocorticoid treatment induced S-phase DNA synthesis. This induction of DNA synthesis was inefficient, and cell proliferation was not evident, suggesting that growth factors act through stimulation of c-myc expression together with other intracellular events.
Mol Cell Biol 1987 Oct
PMID:Growth factor-deprived BALB/c 3T3 murine fibroblasts can enter the S phase after induction of c-myc gene expression. 331 81

cAMP-treated bovine adrenocortical cells are arrested in the G1 phase of the cell cycle. Removal of serum also arrests bovine adrenocortical cells in G1. In the presence of cAMP, serum and fibroblast growth factor stimulate increases in medium cell volume, but DNA synthesis is not initiated. Under these conditions cAMP increases steroidogenic capacity 7- to 10-fold as assessed by metabolism of pregnenolone to fluorogenic steroids. When the kinetics of entry of cells into S phase are quantitated, serum- and FGF-treated cells initiate DNA synthesis at an exponential rate after a 12-h lag. In contrast when cAMP is removed, cells immediately initiate DNA synthesis without a lag at a similar exponential rate (6.3 and 5.3% of the cells entering S/h). In the presence of growth factors, cAMP-treated bovine adrenocortical cells are thus hypertrophied with increased steroidogenic capacity, but are reversibly arrested at the G1/S boundary. These findings suggest that cAMP arrests cell replication by mechanisms distinct from those of serum deprivation.
Mol Cell Endocrinol 1980 Jul
PMID:Kinetics of cAMP inhibition of DNA synthesis in bovine adrenocortical cells. 624 1

Skeletal alpha-actin (SkA) is representative of the cardiac genes that are expressed at high levels in embryonic myocardium, downregulated after birth, and reactivated by tropic signals including basic fibroblast growth factor (FGF-2) and type beta transforming growth factors (TGF beta). To investigate the molecular basis for cardiac-restricted and growth factor-induced SkA transcription, we have undertaken a mutational analysis of the SkA promoter in neonatal ventricular myocytes, with emphasis on the role of three nominal serum response elements. Serum response factor (SRF) and the bifunctional factor YY1 are the predominant cardiac proteins contacting the proximal SRE (SRE1). Mutations of SRE1 that prevent recognition by SRF and YY1. or SRF alone, virtually abolish SkA transcription; mutation of distal SREs was ineffective. A mutation which selectively abrogates YY1 binding increases expression, substantiating the predicted role of YY1 as an inhibitor of SRF effects. SkA transcription requires combinational action of SRE1 with consensus sites for Sp1 and the SV40 enhancer binding protein, TEF-1. As an isolated motif, SRE1 can confer responsiveness to both FGF-2 and TGF beta to a heterologous promoter. Whether TEF-1 binding sites likewise can function as FGF response elements is unknown. Molecular dissection of mechanisms that govern the differentiated cardiac phenotype has largely been undertaken to date in neonatal ventricular myocytes, as the adult ventricular myocyte has been refractory to conventional procedures for gene transfer. To circumvent expected limitations of other methods, we have used replication-deficient adenovirus to achieve efficient gene transfer to adult cardiac cells in culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1994 Sep
PMID:Control of cardiac gene transcription by fibroblast growth factors. 752 25

Basic fibroblast growth factor (FGF-2) is nearly ubiquitous in its distribution, leading numerous investigators to propose that there must exist highly specific mechanisms to regulate its bioavailability. Moreover, in each of the tissues where it can be localized, numerous cells are its potential target. The identification of these mechanisms could serve as an important step in developing novel strategies to inhibit FGF action. It could be possible to block such FGF-dependent activities as angiogenesis, tumor growth, reproduction, and selected diseases of cell proliferation. Over the course of the past several years, we have attempted to describe some of the processes that might regulate a target cell's ability to activate FGF-2 in its local milieu.
Mol Reprod Dev 1994 Sep
PMID:Potential mechanisms regulating the extracellular activities of basic fibroblast growth factor (FGF-2). 752 26

Several heparin-binding growth factors (HBGFs) are thought to play a key role in the natural processes of tissue homeostasis, regeneration or repair. The HBGFs are active upon release from neighbouring inflammatory or circulating cells, as well as upon release from heparan sulfate proteoglycosaminoglycans that are associated with the extracellular matrix (ECM). To better understand the physiological role of these HBGFs, we have focused our effort on studying a subset of HBGFs, namely FGF-1 and FGF-2 and their receptors. We present the purification and characterisation of a new form of heparin-binding FGF receptor from adult bovine brain (Perderiset et al., 1992). This receptor has now been purified to homogeneity. Ligand blot and cross-linking experiments performed with labeled FGF-1 or FGF-2 revealed 80-kd and 130-kd bands. Preliminary sequence information indicates that receptor is different from the receptors, FGFR-1 to -4, but it may be related the cysteine-rich-FGF receptor (CFR). We have previously shown that FGF-1, but not FGF-2, is specifically expressed in myoblastic satellite cells during the proliferating phase preceding myoblast alignment and fusion. We have now transfected primary cultures of rat myoblastic satellite cells with FGF-1 cDNA and expressed this growth factor constitutively. The transfected cells were no longer able to form myotubes. Transfection with antisense FGF-1 induced myotube formation suggesting that endogenous expression of FGF-1 is associated with myoblastic cell differentiation. Numerous studies have concluded that the ECM represents a natural reservoir for various HBGFs.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1994 Sep
PMID:FGFs and their receptors, in vitro and in vivo studies: new FGF receptor in the brain, FGF-1 in muscle, and the use of functional analogues of low-affinity heparin-binding growth factor receptors in tissue repair. 752 27

We reported previously that the mitogenic activities of FGF-1 (acidic FGF) could be dissociated from its receptor-binding activities by site-directed mutagenesis of lysine 132 to a glutamic acid. Although the mutant FGF-1 protein binds to the high-affinity tyrosine-kinase receptors, stimulates tyrosine-kinase activity, and promotes expression of immediate-early genes, it is not mitogenic for a variety of tested cell lines. Interestingly, the mutant FGF-1 is capable of other functions associated with the wild-type protein such as promotion of mesoderm formation in Xenopus animal caps. The mutant exhibits a reduced apparent affinity for heparin-Sepharose compared to the wild-type protein. The relationship between the reduced heparin affinity and lack of mitogenic activity of this mutant is not clear. Recent data indicates the relationship is not as simple as reduced stability of the protein. When NIH 3T3 cells are transfected with expression vectors encoding either wild-type or mutant FGF-1, a transformed phenotype can be seen in cells overexpressing the wild-type FGF-1, whereas cells overexpressing mutant FGF-1 appear normal. Analysis of lysates of these cells indicates that a tyrosine-kinase cascade, distinct from that associated with the high-affinity cell surface receptors, has been activated in the wild-type transfected cells but not in the mutant transfected cells. Although both transfected cell lines contain FGF-1 cell surface receptors as judged by crosslinking studies, the wild-type transfectants are refractory to exogenous FGF-1, whereas the mutant transfectants respond normally.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1994 Sep
PMID:Structure-function studies of FGF-1: dissociation and partial reconstitution of certain of its biological activities. 752 28

We examined the effect of growth hormone on local growth factor mRNA expression in male Sprague-Dawley rats. Repetitive systemic administration of growth hormone (0.4 IU every 4 h) increased the expression of IGF-I mRNA up to 2.8-fold in costal cartilage tissue compared with controls. Basic FGF (bFGF) mRNA expression gradually increased up to 15.5-fold compared with pre-injection samples, where the mRNA expression was 5.3-times greater than vehicle-injected controls. TGF-beta mRNA showed little changes. Moreover, one microgram/ml of growth hormone enhanced the expression of bFGF mRNA in costal chondrocytes in culture. We conclude that growth hormone increased the local expression of bFGF, as well as that of IGF-I, in cartilage, and suggest that bFGF is directly regulated by growth hormone within a local area.
Mol Cell Endocrinol 1995 Jul
PMID:Administration of growth hormone modulates the gene expression of basic fibroblast growth factor in rat costal cartilage, both in vivo and in vitro. 758 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>