Disease relevance of Fgfr4

• However, mice doubly homozygous for disruptions of the fgfr-3 and fgfr-4 genes display novel phenotypes not present in either single mutant, which include pronounced dwarfism and lung abnormalities [1].
• To determine whether FGFR4 expression regulates myoblast differentiation, we infected a soluble dominant-negative FGFR4-containing adenovirus into these cells [2].
• Chronic CCl(4) exposure resulted in severe fibrosis in livers of FGFR4-deficient mice compared to normal mice [3].
• To validate this model in primary human pituitary tumors, we examined the expression of ptd-FGFR4, N-cadherin, and clinical behavior [4].

High impact information on Fgfr4

• 1. Furthermore, the temporal expression and selective inhibition of FGF receptors 1 and 4 present within the endoderm implies that signaling through FGFR4 is involved in specifying lung versus liver [5].
• An examination of fgf receptor gene expression indicated that all four receptors (fgfr-1 to fgfr-4) are expressed in postnatal lungs at varying levels [1].
• FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung [1].
• Fgfr4 is a putative receptor for FGF6 [6].
• These results suggest that FGFR-4 is likely to have diverse roles in development, which may include regulation of definitive endoderm and skeletal muscle lineages [7].

Chemical compound and disease context of Fgfr4

• Increased carbon tetrachloride-induced liver injury and fibrosis in FGFR4-deficient mice [3].

Biological context of Fgfr4

• Responsiveness of developing dental tissues to fibroblast growth factors: expression of splicing alternatives of FGFR1, -2, -3, and of FGFR4; and stimulation of cell proliferation by FGF-2, -4, -8, and -9 [8].
• These results suggest that FGFR4 may be an important regulator of osteogenesis with involvement in preosteoblast proliferation and differentiation as well as osteoblast functioning during intramembranous ossification [9].
• To begin to dissect the molecular pathways involving Fgfr4, we queried the promoter sequences for transcriptional factor binding sites and tested candidate regulators in a 27-time point regeneration series [10].
• Fgfr4 has been shown to be important for appropriate muscle development in chick limb buds; however, Fgfr4 null mice show no phenotype [10].
• FGFR1, FGFR2, and FGFR4 have unique patterns of expression during embryogenesis suggesting that these receptors mediate different functions of FGFs during development [11].

Anatomical context of Fgfr4

• FGFR-4 protein was detected in all cells of the implanting embryo, but was restricted to the ICM/primitive endoderm in later stage outgrowths [12].
• We tested blastocyst outgrowths, a model for implantation, for FGFR-3 and FGFR-4 protein [12].
• Immunocytochemical analysis of primary osteoblast cultures taken from the same cranial region also revealed high levels of FGFR4 expression, suggesting a similar pattern of cellular expression in vivo and in vitro [9].
• We have investigated the expression pattern of FGFR4 in the neonatal mouse calvaria and compared it to the expression pattern in cultures of primary osteoblasts [9].
• Our findings point to distinct transcriptional regulation and action for FGFR4 in differentiating skeletal muscle cells [2].

Associations of Fgfr4 with chemical compounds

• The results demonstrate that transmembrane sensors interface with metabolite-controlled transcription networks and suggest that pericellular matrix-controlled liver FGFR4 in particular may ensure adequate cholesterol for cell structures and signal transduction [13].
• Mutation of tyrosine Y754F in ptd-FGFR4 abrogated the effect of PD173074-mediated inhibition [4].
• One of these regions is within the kinase domain's activation loop, where FGFR-1, but not FGFR-4, bears a key aspartate residue [14].
• Targeting N-Cadherin through Fibroblast Growth Factor Receptor-4: Distinct Pathogenetic and Therapeutic Implications [4].

Regulatory relationships of Fgfr4

• Mesenchymally expressed "c" splice forms of FGF receptors 2 and 3 and FGF receptor 4 were activated by several FGF-8 isoforms [15].
• Furthermore, FGFR-4 induced only a weak tyrosyl phosphorylation of phospholipase C-gamma and no detectable tyrosyl phosphorylation of the SHC adaptor proteins in contrast to FGFR-1 [16].

Other interactions of Fgfr4

• Recombinant FGF-8b and FGF-8c activate the 'c' splice form of FGFR3, and FGFR4, while FGF-8b also efficiently activates 'c' splice form of FGFR2 [17].
• We examined the ability of these proteins to activate alternatively spliced forms of fibroblast growth factor receptors 1-3, and fibroblast growth factor receptor 4 [17].
• Our data suggest a novel MyoD-Tead2-Fgfr4 pathway important for effective muscle regeneration [10].
• Moreover, Sp1 expression correlated with FGFR4-expression in myotubes [2].
• FGFR4 expression was not detected in the intact and crushed nerve as revealed by RT-PCR and RNase protection assay [18].

Analytical, diagnostic and therapeutic context of Fgfr4

• Immunohistochemistry demonstrated that FGFR4 was highly expressed in rudimentary membranous bone and strictly localised to the cellular components (osteoblasts) between the periosteal and endosteal layers [9].
• RT-PCR and Western blotting for FGFR4 confirmed its presence in primary osteoblast cultures [9].
• Granulosa cells from several follicular stages express the receptor for FGFR-4 mRNA as assayed by in situ hybridization [19].
• We have used the polymerase chain reaction to clone from fetal cerebellar RNA a novel member of the fibroblast growth factor receptor family, FGFR-4. cDNAs encoding a full-length receptor were isolated and RNA expression examined in adult and fetal tissues by RNA blot analysis [7].
• Here we show that livers of mice lacking FGFR4 exhibited normal morphology and regenerated normally in response to partial hepatectomy [13].

References