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

To examine the role of fibroblast growth factors on the proliferation present during angiogenic processes, we analyzed the effects of in vitro cell culture with acidic (FGF-1) and basic (FGF-2) fibroblast growth factors on murine peritoneal exudate cell survival. FGF-1 or FGF-2 in the presence of heparin resulted in a significantly greater cell viability for exudate cells at 24 hours of culture relative to heparin alone or medium controls. Cultures supplemented with FGF-1 or FGF-2 plus heparin showed a slight increase in tritiated[3H] thymidine uptake over heparin or medium alone. No specific change in [3H] uridine incorporation or LDH release was detectable between FGF-1, FGF-2, heparin or medium alone cultures. Our results suggest that FGF-1 and FGF-2 may enhance survival both in vitro and in vivo of a subset of peritoneal exudate cells. This attribute may play a role during inflammatory or tumor-like states.
Res Commun Mol Pathol Pharmacol 1996 Jun
PMID:Acidic and basic fibroblast growth factors prolong the in-vitro survival of murine peritoneal macrophages. 882 35

We recently identified a bipartite element in the rat osteocalcin (OC) promoter that confers synergistic induction by fibroblast growth factor receptor 2 (FGF2) and cAMP. A GCAGTCA motif (OCFRE) at -146 to -138 in the OC promoter is necessary for synergy and participates in a FGF2-regulated DNA-protein interaction. We have isolated the FGF-regulated component of this transcriptional response for detailed study. Two or three copies of the OC promoter fragment -154 to -113 with the intact OCFRE confer 10- or 30-fold FGF2-inductive responses, respectively, on the unresponsive basal promoter 92 OCLUC (luciferase reporter) in MC3T3-E1 cells; a single copy is insufficient. As in the native context, induction depends upon an intact OCFRE motif (mutant GCATTTA motifs unresponsive). FGF receptor 1 can mediate activation; expression of this receptor in L6 cells (no endogenous FGF receptors) permits FGF2 induction of (OCFRE)2 92 OCLUC. FGF2 induction of (OCFRE)2 92 OCLUC in MC3T3-E1 cells is not recapitulated by platelet-derived growth factor-BB, epidermal growth factor, insulin-like growth factor I, or transforming growth factor-beta (< 10% the activity of FGF2). OCFRE activation is not inhibited by kinase inhibitors H-89, wortmannin, staurosporine, KN-62, or H-7. However, the phosphoprotein phosphatase inhibitors okadaic acid (OKA), calyculin A, and vanadate decrease FGF induction of (OCFRE)2 92 OCLUC or (OCFRE)3 92 OCLUC, without inhibiting induction of the interstitial collagenase promoter. OKA and calyculin A do not decrease OCFRE DNA-protein interactions, suggesting that important protein-protein interactions are phosphatase regulated. These data provide evidence that; 1) FGF receptors elaborate transcriptional activation signals that functionally differ from those of other receptor tyrosine kinases; 2) an OKA-sensitive phosphatase participates in FGF receptor-dependent activation of the OCFRE; and 3) two transcriptional activation signals are initiated by FGF receptor activation in MC3T3-E1 cells, reflected in the divergent sensitivities of OCFRE and interstitial collagenase promoter induction to OKA and vanadate.
Mol Endocrinol 1996 Aug
PMID:The rat osteocalcin fibroblast growth factor (FGF)-responsive element: an okadaic acid-sensitive, FGF-selective transcriptional response motif. 884 19

Basic fibroblast growth factor (FGF-2) induces cell proliferation and urokinase-type plasminogen activator (uPA) production in fetal bovine aortic endothelial GM 7373 cells. In the present paper we investigated the role of the interaction of FGF-2 with tyrosine-kinase (TK) FGF receptors (FGFRs) in mediating uPA up-regulation in these cells. The results show that FGF-2 antagonists suramin, protamine, heparin, the synthetic peptide FGF-2(112-155), and a soluble form of FGFR-1 do not inhibit FGF-2-mediated uPA up-regulation at concentrations that affect growth factor binding to cell surface receptors and mitogenic activity. In contrast, tyrosine phosphorylation inhibitors and overexpression of a dominant negative TK- mutant of FGFR-1 abolish the uPA-inducing activity of FGF-2, indicating that FGFR and its TK activity are essential in mediating uPA induction. Accordingly, FGF-2 induces uPA up-regulation in Chinese hamster ovary cells transfected with wild-type FGFR-1, -2, -3, or -4 but not with TK- FGFR-1 mutant. Small unilamellar phosphatidyl choline:cholesterol vesicles loaded with FGF-2 increased uPA production in GM 7373 cells in the absence of a mitogenic response. Liposome-encapsulated FGF-2 showed a limited but significant capacity, relative to free FGF-2, to interact with FGFR both at 4 degrees C and 37 degrees C and to be internalized within the cell. uPA up-regulation by liposome-encapsulated FGF-2 was quenched by neutralizing anti-FGF-2 antibodies, indicating that the activity of liposome-delivered FGF-2 is mediated by an extracellular action of the growth factor. Taken together, the data indicate that a distinct interaction of FGF-2 with FGFR, quantitatively and/or qualitatively different from the one that leads to mitogenicity, is responsible for the uPA-inducing activity of the growth factor.
Mol Biol Cell 1996 Mar
PMID:A distinct basic fibroblast growth factor (FGF-2)/FGF receptor interaction distinguishes urokinase-type plasminogen activator induction from mitogenicity in endothelial cells. 886 66

Linear synthetic peptides related to the human Fibroblast Growth Factor-1 (hFGF-1) segment [112-147] were tested for their capacity of mimicking FGF mitogenic activity, binding to heparin-Sepharose columns, stimulating DNA synthesis and competing with hFGF-1 for the cellular receptors. The results obtained indicated that the activity of these compounds is dependent on the presence of the sequence WFVGLK in their structures. The affinity for the cellular receptors increased when this sequence was elongated in order to incorporate amino acid residues that are important for FGF-heparin binding.
Biochem Mol Biol Int 1996 Aug
PMID:Mitogenic activity of peptides related to the sequence of human fibroblast growth factor-1. 887 78

Glia cell line-derived neurotrophic factor (GDNF), a recently cloned member of the transforming growth factor-beta (TGF-beta) superfamily, has been implicated in the survival, morphological and functional differentiation of midbrain dopaminergic neurons and motoneurons in vitro and in vivo. The factor may thus have utility in the treatment of various human neurodegenerative disorders. Mechanisms regulating expression of GDNF in normal and diseased brain as a possible means to increase the local availability of GDNF are only beginning to be explored. We have established and employed a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to study and compare levels of expression of GDNF mRNA in several cell types and to investigate its regulation. GDNF expression was clearly evident in primary cultured astrocytes, the glioma B49 and C6 cell, but less pronounced in the Schwannoma RN22 cell lines. Little or no signal could be observed in neuroblastoma cell lines (IMR32, LAN-1) or the pheochromocytoma cell line PC12, emphasizing the glial character of this factor. Using the C6 cell line we found that fibroblast growth factor-2 (FGF-2; bFGF) can increase GDNF mRNA levels, whereas FGF-1, platelet-derived growth factor (PDGF), and vasoactive intestinal polypeptide (VIP) are apparently ineffective. Several other factors (forskolin, kainic acid, triiodothyronine dexamethasone, GDNF, TGF-beta 1, and interleukin-6) appear to have slightly negative effects on GDNF mRNA levels at the concentrations tested. To further explore the relationship between FGF-2 and GDNF, we also addressed the question whether GDNF, like FGF-2, may have an effect on C6 cell proliferation. We conclude that (1) glial and glial tumor cells, rather than neuronal cell lines, express GDNF, (2) that FGF-2 has a prominent inductive effect on GDNF expression and (3) that GDNF stimulates C6 cell proliferation. Finally, these data suggest that neurotrophic actions of FGF-2 in mixed glial-neuronal cell cultures might be mediated in part by GDNF.
Brain Res Mol Brain Res 1996 Sep 05
PMID:GDNF mRNA levels are induced by FGF-2 in rat C6 glioblastoma cells. 888 50

In this study, we investigated the susceptibility of the growth factors (EGF, bFGF, TGF beta and PDGF) to degradation by the protease elaborated by H. pylori and assessed the effect of antiulcer agents, ebrotidine and sucralfate, on this enzymatic action of the bacterium. The colonies of H. pylori were washed with saline, filtered to retain the bacteria, and the filtrate used as an enzyme source. The assays revealed that while EGF and beta FGF showed only marginal (5-7%) susceptibility to H. pylori protease, a 61.7% degradation occurred with PDGF and 62.3% with TGF beta. Introduction of ebrotidine or sucralfate to the assay system led to the reduction in the rate of growth factors degradation, which at 50 micrograms/ml ebrotidine reached the value of 85.1% for PDGF and 88.6% for TGF beta, while with sucralfate the optimal inhibition of PDGF (79.6%) and TGF beta (82.7%) degradation occurred at 200 micrograms/ml. The results demonstrate that PDGF and TGF beta are susceptible to H. pylori degradation and that antiulcer agents, ebrotidine and sucralfate are capable of counteracting this effect.
Biochem Mol Biol Int 1996 Sep
PMID:Susceptibility of growth factors to degradation by Helicobacter pylori protease: effect of ebrotidine and sucralfate. 888 87

FGFs (fibroblast growth factors) play major roles in a number of developmental processes. Recent studies of several human disorders, and concurrent analysis of gene knock-out and properties of the corresponding recombinant proteins have shown that FGFs and their receptors are prominently involved in the development of the skeletal system in mammals. We have compared the sequences of the nine known mammalian FGFs, FGFs from other vertebrates, and three additional sequences that we extracted from existing databases: two human FGF sequences that we tentatively designated FGF10 and FGF11, and an FGF sequence from Caenorhabditis elegans. Similarly, we have compared the sequences of the four FGF receptor paralogs found in chordates with four non-chordate FGF receptors, including one recently identified in C. elegans. The comparison of FGF and FGF receptor sequences in vertebrates and nonvertebrates shows that the FGF and FGF receptor families have evolved through phases of gene duplications, one of which may have coincided with the emergence of vertebrates, in relation with their new system of body scaffold.
J Mol Evol 1997 Jan
PMID:Of worms and men: an evolutionary perspective on the fibroblast growth factor (FGF) and FGF receptor families. 901 Jan 35

NGFI-B and Ad4BP are steroid hormone receptor-like transcription factor that may control steroidogenesis, growth and differentiation in the adrenal cortex. We have studied the induction of NGFI-B and Ad4BP and mRNAs by the peptide hormones, ACTH, AII, IGF, FGF, and by KCl depolarization in cultured bovine adrenocortical cells. The mRNAs for these two transcription factors were most effectively but differentially induced by ACTH and AII. mRNA for NGFI-B was typically undetectable in unstimulated cells, but rapidly (< 30 min) accumulated in response to ACTH and AII. Peak increases occurred within 2-3 h after which mRNA levels declined. At maximally effective concentrations, AII produced increases in NGFI-B mRNA 2.7-fold larger than those triggered by ACTH (n = 7). In contrast to NGFI-B, Ad4BP mRNA was readily detectable in unstimulated cells. ACTH and AII induced smaller, slower and more sustained increases in Ad4BP mRNA. Peak values were obtained in 6-8 h and Ad4BP mRNA remained elevated for at least 18 h. ACTH produced increases in Ad4BP that were 2.6-fold larger than those stimulated by AII (n = 8). Antagonists of major signaling pathways that couple ACTH and AII receptors to cortisol secretion, including T-type Ca2+ antagonist Ni2+ and penfluridol, the CaM kinase antagonist KN-62, the A-kinase antagonist H-89 and the non-selective kinase antagonist staurosporine, all failed to suppress increases in NGFI-B and Ad4BP mRNAs triggered by these two peptides. Each of these agents effectively inhibited cortisol production stimulated by the peptides. Further, arguing against their proposed role as transcription factors for steroidogenic enzymes, ACTH- and AII-stimulated increases in steroid orphan receptor mRNAs were not correlated with corresponding increases in cortisol production measured over 24 h. The results show that NGFI-B and Ad4BP mRNAs are differentially regulated by ACTH and AII. Only NGFI-B is rapidly and transiently increased with kinetics common to immediate early genes. The lack of correlation between peptide-stimulated increases in orphan receptor mRNAs and cortisol production in combination with the apparent divergence in the associated signaling pathways argue against a primary role for these transcription factors in ACTH- and AII-stimulated steroidogenesis. The dual function of these peptide hormones as mediators of development and corticosteroid synthesis could necessitate the presence of separate, parallel signaling pathways.
Mol Cell Endocrinol 1996 Nov 29
PMID:ACTH and AII differentially stimulate steroid hormone orphan receptor mRNAs in adrenal cortical cells. 902 29

In this report, we have carried out mRNA in situ hybridization analysis to study the pattern of expression of the fibroblast growth factor-2 (FGF-2) gene during chick development. The expression pattern of FGF-2 was compared to that of the fibroblast growth factor-1 (FGF-1) gene to further assess a possible role of the FGF-2 during chick embryogenesis. The whole embryos of various stages were examined with 35S-labeled riboprobes transcribed from the coding regions of chick FGF-2 and FGF-1 cDNAs. We show that the distribution pattern of FGF-2 mRNA was highly specific. The FGF-2 transcripts were localized to limb mesenchymes, pharyngeal regions, and embryonic kidneys in day 3 to day 6 chick embryos. However, no FGF-1 mRNA was detected in these structures indicating a unique role of FGF-2 in chick development. These results support the hypothesis that FGF-2 may be a crucial signaling molecule during chick embryogenesis.
Mol Cells 1997 Apr 30
PMID:Expression of the fibroblast growth factor-2 gene during chick development. 916 34

The present study examines the effects of acidic (FGF-1) and basic (FGF-2) fibroblast growth factors on Leydig cell steroidogenesis by cells from 5-, 21- and 90-day-old rats. These ages represent three distinct time points in Leydig cell development: fetal Leydig cells (day 5), immature Leydig cells (day 21) and adult Leydig cells (day 90). The results demonstrate that the actions of the two growth factors on steroidogenesis are developmentally regulated, and require the presence of heparan sulphate proteoglycans (HSPG). FGF-1 and FGF-2 both had stimulatory effects on basal, but not maximally LH-stimulated, testosterone production by fetal Leydig cells, and both growth factors stimulated basal 5 alpha-androstane-3 alpha, 17 beta-diol production by immature Leydig cells. These effects were mediated by heparan sulphate-proteoglycans (HSPG), as they were blocked by the addition of protamine sulphate and sodium chlorate. FGF-1 and FGF-2 had no effect on basal testosterone production by adult Leydig cells, however, FGF-1 alone inhibited LH-stimulated testosterone production by adult Leydig cells in a dose-dependent manner. These data demonstrate that the effects of FGF-1 and FGF-2 are dependent on the specific stage of Leydig cell differentiation and development and may vary accordingly. Furthermore, although FGF-1 and FGF-2 are closely related structurally, a different effect of these two growth factors can be observed on the same type of Leydig cells. The data therefore suggest that these growth factors may have different but specific roles in the regulation of Leydig cell steroidogenesis, at different stages of development.
J Steroid Biochem Mol Biol 1997 Feb
PMID:Developmental response by Leydig cells to acidic and basic fibroblast growth factor. 919 74


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