Disease relevance of Fgfr1

• This study unequivocally demonstrates coordinate up-regulation and trafficking of FGF-2 and full-length FGFR1 to the nucleus of reactive astrocytes in an in vivo model of brain injury, thereby implicating a role in nuclear activity for these molecules [1].
• A recombinant adenovirus encoding a truncated murine FGFR-1 lacking the kinase domain (DN-FGFR) efficiently expressed the transgene in cultured rat aortic smooth muscle cells [2].
• Within hours after experimental retinal detachment or focal injury, there is a twofold increase in FGFR1 immunoreactivity in the outer nuclear layer that persists for at least 7 days; a similar increase in bFGF immunoreactivity in the interphotoreceptor matrix is also apparent [3].
• These data demonstrate a time course for astrocyte expression of FGFR that precedes and parallels the time course for astrocyte hypertrophy [4].
• Gene expressions of bFGF and FGFR1 were detected in the ganglion cell and inner nuclear layers of the normal adult rat retina [5].

Psychiatry related information on Fgfr1

• Here, we show that intracerebroventricular administration of the FG loop (FGL), a synthetic 15 amino acid peptide corresponding to the binding site of NCAM for the fibroblast growth factor receptor 1 (FGFR1), immediately after training rats in fear conditioning or water maze learning, induced a long-lasting improvement of memory [6].
• Rats subjected to eight cycles of food deprivation and refeeding (MFR group) showed significantly decreased circulating leptin levels when compared with control rats (nearly 50% decrease in leptin levels, P < 0.01) [7].

High impact information on Fgfr1

• In the present study, we demonstrate that activation of NCAM and L1 can lead to phosphorylation of the FGFR [8].
• Both this and the neurite outgrowth response stimulated by all three of the above CAMs are lost when a kinase-deleted, dominant negative form of FGFR1 is expressed in PC12 cells [8].
• These divergent bFGF effects were explained in part by upregulated glomerular bFGF receptor expression, induced by PHN serum [9].
• METHODS: Two tumor cell lines (human DLD-2 colon carcinoma and rat C6 glioma) were characterized for bFGF content and bFGF receptor levels by Western blot analysis in cultured cells and by studies of [125I]rHu-bFGF binding to sections from xenografts grown in nude mice [10].
• Localization of FGF receptor mRNA in the adult rat central nervous system by in situ hybridization [11].

Chemical compound and disease context of Fgfr1

• C6 glioma cells also transcribe message for FGF receptor 1 (FR1), suggesting possible autocrine growth by these cells [12].
• The effects of estradiol (E2) on cell growth and the expression of fibroblast growth factor receptor (FGFR) were investigated in a cultured rat anterior pituitary cell line (MtT/Se) established from an E2-induced mammotropic pituitary tumor [13].
• We have recently cloned and expressed a recombinant gene encoding Pseudomonas exotoxin with a mutated (nonfunctional) cell recognition domain fused with the ligand acidic fibroblast growth factor, termed aFGF-PE66(4Glu)KDEL; thus, this recombinant toxin targets the fibroblast growth factor receptor [14].
• Pancreatic ductal adenocarcinomas (PDACs) overexpress various cell-surface tyrosine kinase receptors, including the type I high-affinity fibroblast growth factor receptor (FGFR-1) [15].
• The effects of HSV-1 amplicon and polyethyleneimine (PEI)-mediated transfection of dominant negative FGF receptor-1 mutant FGFR1(TK-) into the rat brain substantia nigra (SN) were examined in vivo to model the reduced FGF signaling documented to occur in Parkinson's disease [16].

Biological context of Fgfr1

• Ligand binding studies indicated that elastase treatment decreased total binding of (125)I-bFGF to the cell surface and affected both fibroblast growth factor receptor and heparan sulfate proteoglycan (HSPG) binding sites [17].
• Collectively, these results provide compelling evidence for FGFR1 gene expression by rat photoreceptors in situ [3].
• These data demonstrate that inhibition of FGF receptor activation results in apoptosis and suggest that an intact autocrine FGF signaling loop is required for vascular smooth muscle cell survival in vitro [2].
• FGFR1 expression was analyzed immunohistochemically and at the transcription level in single photoreceptor cells, after reverse transcription (RT), using the polymerase chain reaction (PCR) [3].
• Furthermore, we demonstrate that the NCAM module was able to induce activation (phosphorylation) of FGFR and to stimulate neurite outgrowth [18].

Anatomical context of Fgfr1

• For these studies, pulmonary fibroblast cultures were treated with porcine pancreatic elastase, and elastase-mediated changes in bFGF receptor expression and binding profiles were assessed [17].
• However, the precise contribution of nuclear FGF-2/FGFR1 to the pathophysiological response of astrocytes after injury is undetermined [1].
• An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons [19].
• Rapid upregulation of fibroblast growth factor receptor 1 (flg) by rat photoreceptor cells after injury [3].
• In the intact cerebral cortex, FGF-2 and FGFR1 mRNA and protein were constitutively expressed in astrocytes and neurones respectively [20].

Associations of Fgfr1 with chemical compounds

• Expression of FGF-R1 was not affected by exposure to 95% O2 or recovery in air [21].
• Likewise, in PC12E2 cells transiently expressing a dominant-negative form of the mouse FGFR1, induction of neurites by the C3 peptide was abrogated [22].
• Tyrosine autophosphorylation of FGFR upon stimulation by bFGF was significantly higher in scar fibroblasts than in normal palatal fibroblasts [23].
• A striking increase in the bFGF immunoreactivity and a moderate increase in the fibroblast growth factor receptor-1 (FGFR-1) immunoreactivity were also found in the astrocytes treated with serum- or glucose-deprivation or glutamate [24].
• We have examined expression of bFGF and fibroblast growth factor receptor 1 (FGFR-1) in luminal SMCs as well as endothelium at various times after injury, which allowed us to study both replicating as well as quiescent cells [25].

Physical interactions of Fgfr1

• The potent gliogenic and neurotrophic fibroblast growth factor (FGF)-2 signals through a receptor complex comprising high-affinity FGF receptor (FGFR)1 with heparan sulphate proteoglycans (HSPGs) as co-receptors [20].
• Here we show that FGL, a neural cell adhesion molecule (NCAM)-derived peptide binding to and inducing phosphorylation of the fibroblast growth factor receptor (FGFR), acts neuroprotectively after an ischemic insult both in vitro and in vivo [26].
• Characterization of bFGF receptor-binding properties with [125I]bFGF revealed that AR4-2J cells exhibited 2 classes of bFGF binding site with respective KD values of 47 pM and 3 nM and binding capacities of 14 fmol and 0.9 pmol/10(6) cells [27].
• In addition, induced tyrosine phosphorylation of FGFR1 by hydrogen peroxide resulted in complex formation with Grb2 [28].

Enzymatic interactions of Fgfr1

• This 79-kDa FGF receptor was not tyrosine-phosphorylated in response to FGF-1 stimulation, while the 128-kDa FGF receptor was recognized by anti-phosphotyrosine antibody under the same conditions [29].

Co-localisations of Fgfr1

• FGFR1 is colocalized with FGF-2 in the nuclei of reactive astrocytes, and here FGF-2 is associated with nuclear euchromatin [1].
• Fibroblast growth factor receptor 3 expression colocalized with fibroblast growth factor receptor 1 and 2 expression in the chondrocytes and osteoblasts beginning at 10 days of healing, and persisted throughout endochondral bone formation [30].

Regulatory relationships of Fgfr1

• Basic FGF was detected in the nuclei of cells staining for FGFR, suggesting that FGFR-expressing astrocytes also contained bFGF [4].
• Double immunohistochemistry for FGFR and glial fibrillary acidic protein demonstrated that mature astrocytes expressed FGFR [4].
• Egr-1 in turn might play an important role in up-regulating the expression of endo-bFGF which overlapped with the expression of bFGFR to ensure the combination of ligand and receptor to protect against brain ischemia [31].
• A peptide from the first fibronectin domain of NCAM acts as an inverse agonist and stimulates FGF receptor activation, neurite outgrowth and survival [32].
• Stimulation of FGFR-1 activated phospholipase D (PLD) rapidly and transiently, but did not induce PC-specific PLC activity [33].

Other interactions of Fgfr1

• TGF-beta 1 elevated protein and mRNA level of FGF receptor (FGFR) in palatal fibroblasts [23].
• Unlike FGF-2, the distribution of FGFR1 mRNA correlates well with the presence of the immunoreactive receptor [34].
• The findings show that chronic alcohol ingestion exerts detrimental effect on the signaling events initiated by bFGF-receptor activation and propagated by Cdk2 that propels the cell cycle progression essential for rapid mucosal repair [35].
• Gene expression of FGFR-1 was developmentally regulated; expression was higher in prepubertal testes and decreased with sexual maturity [36].
• Immunoreactivity for receptors (R) for IGF-1 and FGF-2 (IGF-1R, FGFR1, and FGFR3) was most pronounced in chondroblasts and hypertrophic chondrocytes, while FGFR2 immunoreactivity was strongest in the articular and prechondroblastic zones [37].

Analytical, diagnostic and therapeutic context of Fgfr1

• Western blot analyses indicated that elastase treatment did not release significant amounts of fibroblast growth factor receptor protein [17].
• Intraperitoneal injection of soluble truncated FGF-R1 at the onset of the recovery phase arrested compensatory lung DNA synthesis and secondary septation seen in control animals after 3 days of recovery, confirming a role for FGF-R1 in this model of compensatory neonatal lung growth [21].
• Although no definitive evidence for the presence of FGFR-1 in normal LHRH neurons could be obtained by either double immunohistochemistry or double in situ hybridization procedures, fetal LHRH neurons in primary culture responded to bFGF with neurite outgrowth [38].
• Real time quantitative RT-PCR was used to measure changes in FGFR1 mRNA levels in the retina in response to injury or detachment [3].
• RESULTS: Confocal immunofluorescence observations showed that FGFR1 immunoreactivity in the rat retina is concentrated primarily in the perinuclear cytoplasm of photoreceptor cell bodies [3].

References