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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We are attempting to develop methods for in vitro culture of zebrafish embryonal stem cells. Primary cultures were initiated from wild-type zebrafish early embryos in basal nutrient medium supplemented with insulin, selenite, leukemia inhibitory factor, trout serum, fetal bovine serum, and trout embryo extract. In this medium, melanocytes appeared on the second day of culture. Basic fibroblast growth factor (bFGF) was mitogenic when cells were plated at low densities. bFGF suppressed melanogenesis is a dose-dependent fashion, with maximal effect at 20 ng/mL. Cultures initiated and maintained with bFGF for 24 hours and then incubated without bFGF for as long as 8 days did not contain pigmented cells. Experiments in which bFGF was added or removed at various times after initiation of cultures indicated that maximum sensitivity to bFGF occurred during the first 12 hours of culture. When wild-type cells from cultures without bFGF were injected into albino blastula-stage embryos, melanocytes subsequently developed in host embryos: no melanocytes appeared when cells from cultures with bFGF were injected into albino hosts.
Mol Mar Biol Biotechnol 1994 Apr
PMID:Basic fibroblast growth factor stimulates proliferation and suppresses melanogenesis in cell cultures derived from early zebrafish embryos. 808 86

Mammary gland development is dependent upon local regulatory factors as well as systemic hormones to mediate gland morphogenesis and associated mesenchymal-epithelial interactions. FGF-3 (int-2) has been implicated as an oncogenic growth factor produced locally in mouse mammary tumor virus-induced mammary tumorigenesis. The observation that FGF-3 is not expressed during normal mammary development as well as the high degree of cellular proliferation and angiogenesis that accompany mammary gland growth suggest roles for other FGF family members in this process. In this study, we have examined expression of FGF family members at various stages of mouse mammary growth and tumorigenesis. FGF-1, FGF-2, FGF-4, and FGF-7 were expressed during the ductal stage of mammary development. The majority of FGF-1 gene expression was in the luminal epithelial cells, whereas FGF-2 expression was in the mammary stroma and possibly the myoepithelial cells. The presence of mammary epithelium induced the expression of both FGF-2 and FGF-7 in the stroma. FGF-1 and FGF-2 expression declined during pregnancy and dropped again during lactation, but quantitative analysis showed a much more dramatic decrease in FGF-2 expression. FGF-7 transcripts were also detected during pregnancy and lactation, but an alternate transcript size was observed at these stages. FGF-1, FGF-2, and FGF-7 transcripts were detected in mammary preneoplasias, tumors, and immortal cell lines, but at levels less than those seen during normal mammary growth. These results support the hypothesis that FGF family members play a role in local regulation of mammary development. The differential spatial and temporal pattern of FGF-1, FGF-2 and FGF-7 gene expression indicate that they each have unique functions in the gland.
Mol Endocrinol 1994 Feb
PMID:Differential temporal and spatial gene expression of fibroblast growth factor family members during mouse mammary gland development. 817 Apr 78

During embryogenesis, the neurons of vertebrate sympathetic and sensory ganglia become dependent on neurotrophic factors, derived from their targets, for survival and maintenance of differentiated functions. Many of these interactions are mediated by the neurotrophins NGF, BDNF, and NT3 and the receptor tyrosine kinases encoded by genes of the trk family. Both sympathetic and sensory neurons undergo developmental changes in their responsiveness to NGF, the first neurotrophin to be identified and characterized. Subpopulations of sensory neurons do not require NGF for survival, but respond instead to BDNF or NT3 with enhanced survival. In addition to their classic effects on neuron survival, neurotrophins influence the differentiation and proliferation of neural crest-derived neuronal precursors. In both sympathetic and sensory systems, production of neurotrophins by target cells and expression of neurotrophin receptors by neurons are correlated temporally and spatially with innervation patterns. In vitro, embryonic sympathetic neurons require exposure to environmental cues, such as basic FGF and retinoic acid to acquire neurotrophin-responsiveness; in contrast, embryonic sensory neurons acquire neurotrophin-responsiveness on schedule in the absence of these molecules.
Mol Neurobiol
PMID:Development of trophic interactions in the vertebrate peripheral nervous system. 817 44

A composite procedure involving molecular modelling and a property-pattern algorithm, the Resonant Recognition Model (RRM), has been applied to structure-function studies with basic fibroblast growth factor (bFGF). Property-pattern characteristics for biological activity and receptor recognition for a group of FGF-related proteins were defined and then used to aid the design of a set of peptides which can act as bFGF antagonists. Molecular modelling techniques were then employed to identify the peptide within this set with the greatest conformational similarity to the putative receptor domain of bFGF. This 16 amino acid residue peptide (16mer), which exhibits no sequence homology to bFGF, antagonised the stimulatory effect of bFGF on fibroblast [3H]thymidine incorporation and cell proliferation, but exerted no effect itself in these in vitro bioassays.
Mol Cell Biochem 1994 Jan 12
PMID:In vitro inhibition of the actions of basic FGF by a novel 16 amino acid peptide. 819 Jan 16

Insulin-like growth factor-I (IGF-I), by itself, cannot sustain the growth of BALB/c 3T3 cells, but requires the cooperation of other growth factors, such as platelet-derived growth factor or epidermal growth factor. In 3T3 cells constitutively overexpressing the human IGF-I receptor, called p6 cells, IGF-I by itself is fully mitogenic. We show here that p6 cells are also stimulated to enter DNA synthesis by the sole addition of basic fibroblast growth factor (bFGF), which, by itself, is incapable of stimulating parental 3T3 cells. Although bFGF does not bind directly to the IGF-I receptor, it induces its autophosphorylation. Stimulation of p6 cells by bFGF is not inhibited by an antibody to the IGF-I receptor that inhibits IGF-I-mediated DNA synthesis, and IGF-I is not detectable in the medium of bFGF-treated p6 cells. Stimulation cannot be explained by an increased number of FGF receptors, because p6 cells actually have slightly fewer FGF receptors than parental BALB/c 3T3 cells. Basic FGF also stimulates DNA synthesis in 3T3 cells overexpressing a mutant IGF-I receptor that does not autophosphorylate in response to IGF-I and has lost its mitogenic potential. Although we were unable to demonstrate directly that bFGF causes transphosphorylation of the IGF-I receptor, we conclude that in cells overexpressing the IGF-I receptor, bFGF can stimulate DNA synthesis either by an unknown mechanism or through transphosphorylation of the IGF-I receptor.
Mol Endocrinol 1993 Sep
PMID:Basic fibroblast growth factor stimulates DNA synthesis in cells overexpressing the insulin-like growth factor-I receptor. 824 18

A differentiated liver cell (HepG2), which exhibits a dose-dependent growth-stimulatory and growth-inhibitory response to heparin-binding fibroblast growth factor type 1 (FGF-1), displays high- and low-affinity receptor phenotypes and expresses specific combinatorial splice variants alpha 1, beta 1, and alpha 2 of the FGF receptor (FGF-R) gene (flg). The extracellular domains of the alpha and beta variants consist of three and two immunoglobulin loops, respectively, while the intracellular variants consist of a tyrosine kinase (type 1) isoform and a kinase-defective (type 2) isoform. The type 2 isoform is also devoid of the two major intracellular tyrosine autophosphorylation sites (Tyr-653 and Tyr-766) in the type 1 kinase. An analysis of ligand affinity, dimerization, autophosphorylation, and interaction with src homology region 2 (SH2) substrates of the recombinant alpha 1, beta 1, and alpha 2 isoforms was carried out to determine whether dimerization of the combinatorial splice variants might explain the dose-dependent opposite mitogenic effects of FGF. Scatchard analysis indicated that the alpha and beta isoforms exhibit low and high affinity for ligand, respectively. The three combinatorial splice variants dimerized in all combinations. FGF enhanced dimerization and kinase activity, as assessed by receptor autophosphorylation. Phosphopeptide analysis revealed that phosphorylation of Tyr-653 was reduced relative to phosphorylation of Tyr-766 in the type 1 kinase component of heterodimers of the type 1 and type 2 isoforms. The SH2 domain substrate, phospholipase C gamma 1 (PLC gamma 1), associated with the phosphorylated type 1-type 2 heterodimers but was phosphorylated only in preparations containing the type 1 kinase homodimer. The results suggest that phosphorylation of Tyr-653 within the kinase catalytic domain, but not Tyr-766 in the COOH-terminal domain, may be stringently dependent on a trans intermolecular mechanism within FGF-R kinase homodimers. Although phosphotyrosine 766 is sufficient for interaction of PLC gamma 1 and other SH2 substrates with the FGF-R kinase, phosphorylation and presumably activation of substrates require the kinase homodimer and phosphorylation of Tyr-653. We propose that complexes of phosphotyrosine 766 kinase monomers and SH2 domain signal transducers may constitute unactivated presignal complexes whose active or inactive fate depends on homodimerization with a kinase or heterodimerization with a kinase-defective monomer, respectively. The results suggest a mechanism for control of signal transduction by different concentrations of ligand through heterodimerization of combinatorial splice variants from the same receptor gene.
Mol Cell Biol 1993 Jul
PMID:Control of fibroblast growth factor receptor kinase signal transduction by heterodimerization of combinatorial splice variants. 832 Nov 98

Glia-activating factor (GAF) is a novel heparin-binding growth factor purified from the culture supernatant of a human glioma cell line. It shows a spectrum of activity slightly different from those of other known growth factors. We have isolated the cDNA which encodes human GAF. A homology search revealed that GAF would be the ninth member of the FGF family, and we therefore call it FGF-9. The human FGF-9 cDNA cloned by using oligonucleotide probes encoded a polypeptide consisting of 208 amino acids. Sequence similarity to other members of the FGF family was estimated to be around 30%. Two cysteine residues and other consensus sequences in family members were also well conserved in the FGF-9 sequence. FGF-9 was found to have no typical signal sequence in its N terminus like those in acidic FGF and basic FGF. Acidic FGF and basic FGF are known not to be secreted from cells in a conventional manner. However, FGF-9 was found to be secreted from cells after synthesis despite its lack of a typical signal sequence. It could be detected exclusively in the culture medium of cDNA-transfected COS cells. The amino acid sequence of proteins purified from culture supernatant of the CHO cell line, which was cDNA transfected and selected as a high producer of FGF-9, showed that no peptides were cleaved from the N terminus except the initiation methionine. The rat FGF-9 cDNA was also cloned, and the structural analysis indicated that the PGF-9 gene is highly conserved. Expression of the FGF-9 gene could be detected in the brain and kidney of the adult rat. Restricted gene expression in organs and the unique secretion nature of the protein suggest that FGF-9 plays a physiological role which differs from those of well-characterized acidic FGF and basic FGF.
Mol Cell Biol 1993 Jul
PMID:Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property. 832 Dec 27

Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are two neurotrophic factors that play a role in neuronal maintenance and repair. The identification and characterization of mechanisms regulating neurotrophic factor availability in the central nervous system are vital to the development of therapeutic tools for prevention of neuronal degeneration. The lipophilic beta-adrenergic receptor (BAR) agonist clenbuterol was used to assess whether activation of central BAR changes the levels of NGF and bFGF mRNA. Within 5 hr, clenbuterol (10 mg/kg, intraperitoneally) elicited a 2-3-fold increase in bFGF and NGF mRNA content in rat cerebral cortex. The induction of bFGF and NGF mRNA expression showed anatomical specificity. Among the various brain areas examined, bFGF mRNA levels were increased in the cerebral cortex, hippocampus, and cerebellum, whereas induction of NGF mRNA was observed only in the cerebral cortex. Isoproterenol, a BAR agonist that does not cross the blood-brain barrier, also elicited a 2-3-fold increase in bFGF and NGF mRNA in the cerebral cortex. Propranolol (5 mg/kg, intraperitoneally), a lipophilic BAR antagonist, blocked the induction of NGF and bFGF mRNA mediated by either isoproterenol or clenbuterol, whereas nadolol (5 mg/kg, intraperitoneally), a BAR antagonist that does not cross the blood-brain barrier, blocked only the effect of isoproterenol. Therefore, activation of both central and peripheral BAR play a role in the regulation of bFGF and NGF mRNA expression. Moreover, in adrenalectomized rats, isoproterenol failed to increase bFGF and NGF mRNA, whereas clenbuterol elicited a 2-fold increase in bFGF mRNA in the cortex and hippocampus. Our data suggest that both adrenal steroids and noradrenaline might regulate the availability of selective neurotrophic factors in the adult central nervous system.
Mol Pharmacol 1993 Feb
PMID:Regulation of basic fibroblast growth factor and nerve growth factor mRNA by beta-adrenergic receptor activation and adrenal steroids in rat central nervous system. 838 5

An endothelial cell line (M40) resistant to growth inhibition by transforming growth factor-beta type 1 (TGF beta 1) was isolated by chemical mutagenesis and growth in the presence of TGF beta 1. Like normal endothelial cells, this mutant is characterized by high expression of type II TGF beta receptor and low expression of type I TGF beta receptor. However, the mutant cells display a type II TGF beta receptor of reduced molecular weight as a result of a general defect in N-glycosylation of proteins. The alteration does not impair TGF beta 1 binding to cell surface receptors or the ability of TGF beta 1 to induce fibronectin or plasminogen activator inhibitor-type I production. M40 cells were also resistant to growth inhibition by tumor necrosis factor alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) but were inhibited by interferon-gamma (IFN gamma) and heparin. These results imply that TGF beta 1, TNF alpha, and IL-1 alpha act through signal transducing pathways that are separate from pathways for IFN gamma and heparin. Basic fibroblast growth factor was still mitogenic for M40, further suggesting that TGF beta 1, TNF alpha, and IL-1 alpha act by direct inhibition of cell growth rather than by interfering with growth stimulatory pathways.
Mol Biol Cell 1993 Feb
PMID:A glycosylation-deficient endothelial cell mutant with modified responses to transforming growth factor-beta and other growth inhibitory cytokines: evidence for multiple growth inhibitory signal transduction pathways. 838 75

Using a polyclonal antibody against VGF, we examined the effects of various agents for its expression in PC12h cells. The results obtained were follows; 1) Basic fibroblast growth factor (bFGF), forskolin, dibutyryl cyclic AMP (dbcAMP), and nerve growth factor (NGF) induced the VGF protein. 2) The induction of VGF protein by NGF was inhibited by methylthioadenosine (MTA), but its induction by bFGF was not. 3) The induction of VGF protein by NGF was blocked by staurosporine, but its induction by bFGF was not. These findings suggest that the induction of VGF by NGF is distinct from that by bFGF in terms of sensitivities to MTA and staurosporine.
Biochem Mol Biol Int 1993 Jun
PMID:The signal transduction pathway for VGF expression due to NGF is different from that due to bFGF in PC12h cell. 839 23


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