Disease relevance of FGFR1

• These results suggest that the FGF receptor might act in the transmitter stability, and the plasticity of synapses and ganglion cell axons in adult retina [1].
• Taken together, these data suggest that short-term hypoxia activates endothelial cell proliferation in part via tyrosine phosphorylation of cellular proteins and changes in the expression of the FGF receptor [2].

High impact information on FGFR1

• Control of fibroblast growth factor receptor kinase signal transduction by heterodimerization of combinatorial splice variants [3].
• FGFR2 interacts with a higher apparent affinity than FGFR1 despite both involving 6-O-, 2-O-, and N-sulfates [4].
• This mechanism, which we have named integrative nuclear FGF receptor-1 signaling, involves the nuclear translocation of FGF receptor-1 and its subsequent transactivation of the AII-responsive element in the FGF-2 promoter [5].
• Fibroblast growth factor receptor-1-mediated endothelial cell proliferation is dependent on the Src homology (SH) 2/SH3 domain-containing adaptor protein Crk [6].
• In aged RPE cells, FGFR1 was rapidly activated, and its autophosphorylation followed the kinetics of endogenous FGF1 secretion, before the onset of apoptosis [7].

Biological context of FGFR1

• We report that heparinase treatment of bovine smooth muscle cells inhibits the binding of (125)I-FGF-2 to FGFR1, but does not inhibit FGF-2 induced cellular proliferation [8].
• Hence, FGFR1 and FGFR2 bind to heparin chains with markedly different kinetics and affinities [4].
• 125I-FGF-2 cross-linking to nuclear extracts followed by FGFR1 immunoprecipitation showed that FGFR1 can account for the nuclear FGF-2 binding sites [9].
• Secreted FGF1 induced long-term activation of FGFR1 and ERK2, which was necessary to induce a constant and high level of Bcl-x production, and to induce cell survival in FGFI cells [10].
• Addition of the anti-FGF receptor 1 antibody (FGFR1 Ab) reverted the transformed phenotype of sp-FGF-1 transfectants [11].

Anatomical context of FGFR1

• Heparan sulphate glycosaminoglycans derived from endothelial cells and smooth muscle cells differentially modulate fibroblast growth factor-2 biological activity through fibroblast growth factor receptor-1 [12].
• Nuclear subfractionation followed by Western blot or immunoelectron microscopic analysis showed that the nuclear FGFR1 is contained in the nuclear matrix and the nucleoplasm [9].
• This may contribute to the cross talk among intracellular signaling pathways activated by FGFR1 and alpha(v)beta(3) integrin in endothelial cells [13].
• Promoter transactivation by HMWFGF-2 was accompanied by an up-regulation of FGFR1 specifically in the cell nucleus and was prevented FGFR1(TK-) but not by IP6 or suramin [14].
• The TH promoter was also transactivated by co-transfected wild-type FGFR1, which localizes to both to the nucleus and the plasma membrane, and by an exclusively nuclear, soluble FGFR1(SP-/NLS) mutant with an inserted nuclear localization signal [14].

Associations of FGFR1 with chemical compounds

• On the surface of smooth muscle cells there are two types of receptors for the mitogenic and angiogenic growth factor fibroblast growth factor-2 (FGF-2); a high affinity tyrosine kinase FGF receptor (FGFR1) and low affinity heparin./heparan-like glycosaminoglycan (HLGAG) component of surface expressed proteoglycans [8].
• Agents that induce translocation of endogenous FGF-2 to the nucleus (forskolin, carbachol, or angiotensin II) increased the intranuclear accumulation of FGFR1 [9].
• These effects were due to the release of fibroblast growth factor 2 (FGF2) stored in the extracellular matrix but not to direct interactions with FGF receptors since V189 was inefficient on heparan sulfate-deficient cells expressing constitutively FGF-R1 [15].
• The studies included the effect of genistein on DNA synthesis, cell viability, phosphotyrosine induction and characterization of the FGF receptor (FGFR) [16].
• Furthermore, FGF-R mRNA was significantly upregulated at 2 hr after PGF2alpha, when compared with the control group [17].

Other interactions of FGFR1

• Moreover, the data show that TRPC subunits are not tyrosine-phosphorylated after bFGF stimulation and they do not co-immunoprecipitate with the type 1 FGF receptor [18].
• It is believed that all three components; FGFR1, FGF-2, and the HLGAG chains, must form a ternary complex for maximal cellular stimulation [8].
• Additionally the expression of fibroblast growth factor receptor (FGFR) and growth hormone receptor (GHR) was investigated [19].
• The expression of FGFR 1, 2 and 3 but not FGFR 4 was detected in bovine lens epithelial cells [20].
• FGF receptor 1 and beta-actin mRNA levels were unchanged [21].

Analytical, diagnostic and therapeutic context of FGFR1

• Western blot analysis demonstrated the presence of 103-, 118-, and 145-kDa forms of FGFR1 in nuclei isolated from BAMC [9].
• Immunocytochemistry with the use of confocal and electron microscopes demonstrated the presence of FGFR1 within the nuclear interior [9].
• IgM anti-FGFR1 binding specificity and immunologic activity were determined by enzyme-linked immunosorbant assay (ELISA) [22].
• Reverse transcription-polymerase chain reaction (RT-PCR) indicated expression of alphaA- and betaB2-crystallin, fibroblast growth factor receptor 1 (FGFR1), and major intrinsic protein (MIP26) in exponential growth [23].
• Receptor trafficking in live cells was studied by confocal microscopy via C-terminal FGFR1 fusions to enhanced green fluorescent protein (EGFP) and confirmed by subcellular fractionation and Western immunoblotting [24].

References