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

In order to further investigate the involvement of FGF1 and FGF2 in the transitional cell carcinoma of the bladder (TCC), we compared the expression of FGF1, FGF2 and their membrane binding sites by biochemical and immunological methods in both human normal urothelium and transitional cell carcinoma of the bladder. Using a specific enzyme immunoassay (EIA), we observed that neoplastic tissue exhibited a lower FGF2 content than normal tissue. FGF1 and FGF2 Western-blot analysis revealed in both types of tissues a major FGF1 form with a low molecular weight (14 kDa) and a single FGF2 form (21 kDa). Immunohistological studies showed that FGF1 was specifically located in normal or transformed urothelial cells, while FGF2 was associated with bladder stroma. Binding analysis in tissue membrane preparations revealed a dramatic drop in both high and low affinity binding sites for FGF2 in TCC bladder in comparison to normal bladder. FGF2 cross-linking experiments illustrated a qualitative modification of FGF2 binding complexes in tumors. These data suggest that invasive bladder carcinoma is associated with modifications of FGF1 and FGF2 tissue levels and alterations in the characteristics of the FGF2 membrane binding sites.
Cell Mol Biol (Noisy-le-grand) 1995 Jun
PMID:Fibroblast growth factors and their specific binding sites in normal urothelium and transitional cell carcinoma (TCC) of the human bladder. 754 93

The fibroblast growth factors (FGFs) fall into two distinct groups with respect to their mode of release from cells. Whereas FGF1 and FGF2 lack conventional signal peptides, the remaining members have typical features of secreted proteins. However, the behavior of mouse FGF3 is anomalous, since, despite entering the secretory pathway and undergoing primary glycosylation, its release from transfected COS-1 cells is very inefficient compared with that of FGF4 and FGF5. To investigate the unusual properties of FGF3, we analyzed the processing, secretion, and intracellular localization of a series of site-directed mutants as well as chimeras produced by fusing parts of FGF3, FGF4, and FGF5. Wild-type FGF3 was shown to accumulate in an immature form in the Golgi complex, from where it is slowly released into the extracellular matrix. Removing or relocating the Asn-linked glycosylation site further impaired its release, and exchanging the signal peptide or carboxy terminus had little effect. In contrast, a chimeric protein with an amino terminus from FGF5 was efficiently secreted and biologically active in cell transformation assays. The data suggest that a structural feature of FGF3 involving the amino-terminal region and glycosylation site has a significant bearing on its passage through the Golgi complex and may regulate the secretion of the ligand.
Mol Cell Biol 1993 Sep
PMID:Retention of fibroblast growth factor 3 in the Golgi complex may regulate its export from cells. 835 14

Tyrosine phosphorylation is key to the differentiation of oligodendrocytes, as the FGF2 and PDGF receptor tyrosine kinases are known to mediate the proliferation and maintenance of their precursors. Marked changes in the levels and localization of tyrosine-phosphorylated proteins were found to accompany differentiation in the CG4 rat oligodendrocyte cell line. These alterations in phosphorylation as well as other differentiation-specific changes were found to be sensitive to inhibition by a tyrosine phosphatase inhibitor. This suggested that at some point early in the differentiation process, tyrosine phosphatases are important. A differential display strategy revealed 11 distinct tyrosine phosphatases in the oligodendrocyte lineage, with both precursor cells and oligodendrocytes expressing four major phosphatase transcripts: PTP alpha, PTP zeta, PTP sigma, and PTP gamma. A majority of the phosphatases examined show an increase in their mRNA levels during differentiation, with a striking upregulation observed for PTP epsilon. Our results suggest a significant role for this class of signal transducers in oligodendrocyte differentiation.
Mol Cell Neurosci 1996 May
PMID:Regulation of tyrosine phosphorylation and protein tyrosine phosphatases during oligodendrocyte differentiation. 881 65

Basic fibroblast growth factor (bFGF, FGF2) controls cell proliferation and differentiation in many organs and tissues. In the ovary, cells proliferate and differentiate during folliculogenesis and during formation of the corpus luteum. While previous studies have inferred a role for bFGF in these processes, the precise contribution of bFGF to follicular activation or recruitment has not been established. For this reason, bFGF was immunolocalized in bovine follicles, using anti-bFGF immunoglobulin specific for the 1-24-amino acid terminus of the 18-kDa peptide. Basic FGF was immunolocalized to the cytoplasm of oocytes from bovine primordial and primary follicles. Strong immunostaining was also observed in corpora lutea, the ovarian surface epithelium, and smooth muscle cells surrounding blood vessels, while substantial levels of immunostaining were also present in cells of the theca interna. In most of the healthy antral follicles examined, the three or so layers of granulosa cells which were closest to the basement membrane were also stained, with greatest levels of staining at the most basal region of each cell. Atretic antral follicles had significant and uniform levels of immunostaining throughout the theca interna and the membrana granulosa. Immunostaining as described above was reduced to background levels when the primary specific immunoglobulin was preabsorbed with a 350 molar excess of peptide comprising the NH2-terminal 24 amino acids of bFGF. Based upon our previous observations and those reported here, we propose that basic fibroblast growth factor is synthesized by immature oocytes, especially those from primordial and primary follicles, and that bFGF has a potential role in activating follicle growth via stimulation of granulosa cell proliferation and follicular basement membrane synthesis.
Mol Cell Endocrinol 1995 Dec 29
PMID:Immunohistochemical localization of basic fibroblast growth factor in bovine ovarian follicles. 882 88

Interstitial collagenases participate in the remodeling of skeletal matrix and are regulated by fibroblast growth factor (FGF). A 0.2-kb fragment of the proximal human interstitial collagenase [matrix metalloproteinase (MMP1)] promoter conveys 4- to 8-fold induction of a luciferase reporter in response to FGF2 in MC3T3-E1 osteoblasts. By 5'-deletion, this response maps to nucleotides -100 to -50 relative to the transcription initiation site. The 63- bp MMP1 promoter fragment -123 to -61 confers this FGF2 response on the rous sarcoma virus minimal promoter. Intact Ets and AP1 cognates in this element are both required for responsiveness. The AP1 site supports basal and FGF-inducible promoter activity. The intact Ets cognate represses basal transcriptional activity in both heterologous and native promoter contexts and is also required for FGF activation. FGF2 up-regulates a DNA-binding activity that recognizes the MMP1 AP1 cognate and contains immunoreactive Fra1 and c-Jun. Both constitutive and FGF-inducible DNA-binding activities are present in MC3T3-E1 cells that recognize the MMP1 Ets cognate; prototypic Ets transcriptional activators are not present in these complexes. Inhibitors of protein kinase C, phosphatidyl inositol 3-OH kinase, and calmodulin-dependent protein kinase do not attenuate MMP1 promoter activation. FGF2 activates ERK1/ERK2 signaling in osteoblasts; however, 25 microM MAPK-ERK kinase (MEK) inhibitor PD98059 (inhibits by > 85% the phosphorylation of ERK1/ERK2) has no effect on MMP1 promoter activation by FGF2. Ligand-activated and constitutively active FGF receptors initiate MMP1 induction. Dominant negative Ras abrogates MMP1 induction by constitutively active FGFR2-ROS, but dominant negative Rho and Rac do not inhibit induction. The mitogen-activated protein kinase (MAPK) phosphatase MKP2 [inactivates extracellular regulated kinase (ERK) = Jun N-terminal kinase (JNK) > p38 MAPK] completely abrogates MMP1 activation, whereas PAC1 (inactivates ERK = p38 > JNK) attenuates but does not completely prevent induction. Thus, a Ras- and MKP2-regulated MAPK pathway, independent of ERK1/ERK2 MAPK activity, mediates FGF2 transcriptional activation of MMP1 in MC3T3-E1 osteoblasts, converging upon the bipartite Ets-AP1 element. The DNA-protein interactions and signal cascades mediating FGF induction of the MMP1 promoter are distinct from two other recently described FGF response elements: the MMP1 promoter (-123 to -61) represents a third FGF-activated transcriptional unit.
Mol Endocrinol 1997 Jul
PMID:Fibroblast growth factor receptor signaling activates the human interstitial collagenase promoter via the bipartite Ets-AP1 element. 921 60

Overexpression of Alzheimer amyloid precursor protein (APP) produces dramatically different phenotypes in transgenic mice depending on the genetic background. For example, concentrations of APP that produce amyloid plaques in outbred transgenic lines are lethal for inbred FVB/N or C57BL/6J mice. Expression of SOD1 transgenes is protective, suggesting involvement of oxidative damage in premature death, but ablation of Apoe had no significant effect. In contrast, FGF2 transgene overexpression enhances the lethal effects of APP. Differential survival does not appear to reflect genetic differences in APP processing, but rather host responses to APP or its derivatives.
Hum Mol Genet 1997 Oct
PMID:Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice. 930 76

Stimulation of glucocorticoid or beta-adrenergic receptors (BAR) has been shown to increase nerve growth factor (NGF) biosynthesis in adult rat brain. Little is known about the role of these receptors in the regulation of NGF expression in neonatal and aged brain. We have examined the effect of the synthetic glucocorticoid dexamethasone (DEX) and the BAR agonist clenbuterol (CLE) on the levels of NGF mRNA in neonatal (8 day old), adult (3 month old) and aged (24 month old) rats. By 3 h, DEX (0.5 mg/kg, s.c.) evoked a comparable increase in NGF mRNA in the cerebral cortex and hippocampus in both 8-day and 3-month-old rats. In contrast, CLE (10 mg/kg, i.p.) failed to change NGF mRNA levels in neonatal rats, while increasing (2-3-fold) NGF mRNA levels in the cerebral cortex of adult rats. In 24-month-old rats, both DEX and CLE elicited only a modest increase in NGF mRNA. This increase was, however, anatomically and temporally similar to that observed in adult animals. The weak effect of DEX or CLE was not related to a down-regulation of receptor function because both DEX and CLE were able to elicit a comparable increase in the mRNA levels for basic fibroblast growth factor (FGF2) in neonatal, adult and aged rat brain. Our data demonstrate that induction of NGF expression by neurotransmitter/hormone receptor activation varies throughout life and suggest that pharmacological agents might be useful tools to enhance trophic support in aging.
Brain Res Mol Brain Res 1998 Jan
PMID:Differential induction of nerve growth factor and basic fibroblast growth factor mRNA in neonatal and aged rat brain. 947 77

Double electrode voltage clamp technique was used to follow precisely the calcium signalling pathway activated by FGF receptors from a normal and a carcinogenous cell environment. Functional FGF receptors were expressed in Xenopus oocytes following either the injection of PFR1 cRNA from Pleurodeles, an homologue of the human FGFR1 mRNA, or breast cancer MCF7 cells total mRNA. Cytosolic calcium oscillations were monitored through the endogenous Ca(2+)-dependent Cl- channel activity from both RNA injected systems, under FGF2 treatment. The Ca(2+)-dependent Cl- channel was demonstrated using the Cl- channel blocker SITS (250 microM) and by the determination of the reversal potential of the Cl- ions close to -20 mV. The FGF2-evoked Ca(2+)-dependent Cl- current was abolished by external application of genistein (10 microM, tyrosine kinase inhibitor), neomycin (10 mM, phosphatidylinositol turnover inhibitor), caffeine (10 mM, inhibitor of Ins(1,4,5)P3-mediated release of intracellular calcium), and injection of BAPTA (50 microM, calcium chelator) or heparin (2 micrograms/ml, inhibitor of the binding of Ins(1,4,5)P3). The recorded current was independent of extracellular Ca2+ but involved tyrosine kinase phosphorylation and intracellular Ins(1,4,5)P3 sensitive stores. External application of heparin enhanced the oscillatory Ca2+ rise, suggesting a role for the heparan sulfates in the regulatory mechanism of the FGF receptors. The similarities in the Ca(2+)-dependent Cl- current obtained in PFR1 and total MCF7 FGF receptors expressing oocytes are discussed.
Mol Membr Biol
PMID:Ca2+ oscillations induced by fibroblast growth factor 2 in Xenopus oocytes expressing fibroblast growth factor receptors. 949 72

We have used a quantitative RT-PCR approach to determine the levels of Brn3a and Brn3b POU domain transcription factor mRNAs in the developing mouse trigeminal ganglion from E10 to E18. Using low density neuronal cultures, we have shown that NT-3 can regulate the expression of Brn3a mRNA in trigeminal neurons during the periods that they are differentiating and innervating their peripheral and central targets. In contrast to Brn3a, Brn3b mRNA is expressed at extremely low levels in the early trigeminal ganglion. Trigeminal neurons from early ganglia express low levels of Brn3b mRNA in culture and do not up-regulate Brn3b mRNA in response to a number of growth factors and experimental conditions. However, at later ages, when in vivo levels of Brn3b mRNA are high, FGF2, TGFbeta1 and retinoic acid all up-regulate Brn3b mRNA expression in cultured trigeminal neurons. Since NT-3 regulates the developmental expression of Brn3a, Brn3a may mediate some of the effects that NT-3 exerts on sensory neurons and their progenitors. Similarly, Brn3b may mediate some of the effects that FGF2, TGFbeta1 and retinoic acid have on neurons.
Brain Res Mol Brain Res 1998 Apr
PMID:NT-3 regulates expression of Brn3a but not Brn3b in developing mouse trigeminal sensory neurons. 958 31

The rat Nb2-11C lymphoma cell line expresses high affinity prolactin (PRL) receptors, and requires lactogenic hormones for survival and proliferation. We have applied differential display to identify genes which are differentially induced in Nb2-11C cells following PRL stimulation, or which are constitutively expressed in the PRL-independent Nb2-Sp cells. In the present study we characterized a clone (22c.2) which was expressed in Nb2-Sp cells, and in Nb2-11C cells given PRL for 3 h but not in untreated cells. The 279 bp cDNA had 95% homology with the 3' end of the murine 2.6 kb FGF-inducible gene 14 (FIN14). When clone 22c.2 was used to screen a Nb2-Sp cDNA library to obtain a longer cDNA, a unique 1039 bp clone PNR (Prolactin-responsive/ NonO-Related) was isolated, subcloned and sequenced. The deduced amino acid sequence encoded by the PNR open reading frame had significant homology with a family of RNA- and DNA-binding proteins which include the human polypyrimidine tract-binding protein (PTB)-associated splicing factor (PSF), the murine non-POU-domain-containing octamer-binding protein (NonO) and the human NonO homologue p54nrb. Nb2-11C cells expressed three PNR-related mRNA transcripts of 2.5, 3.0 and > 10 kb. Expression of the 2.5 and 3.0 kb transcripts were increased at least 4-fold within 3 h of PRL treatment. PNR expression was also significantly stimulated within 3 h by addition of FGF-2 to either Nb2-11C or Nb2-Sp cells, although alone FGF-2 was not mitogenic for either cell line. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed the expression of both FGF-2 and FGF receptor mRNA in Nb2 cells. raising the possibility of an autocrine or paracrine function for FGF-2 in lymphoma cells. Furthermore, PRL rapidly stimulated the expression of FGF-2 mRNA in a time- and dose-dependent manner in both Nb2-11C and Nb2-Sp cells. FGF-2 expression was increased within 1 h and was maintained at a high level for at least 10 h following treatment with 2 ng/ml PRL. Western blotting with anti-FGF2 antisera demonstrated PRL stimulation of intracellular accumulation, but not secretion of immunoreactive FGF-2. The observation of PRL-responsive expression of FGF-2 in Nb2 cells suggests a previously unrecognized pathway for PRL action in lymphoid cells.
Mol Cell Endocrinol 1998 Feb
PMID:Prolactin induces expression of FGF-2 and a novel FGF-responsive NonO/p54nrb-related mRNA in rat lymphoma cells. 960 21


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