Disease relevance of Fgfr2

• The importance of this splicing choice is highlighted by studies which indicate that deregulation of the FGF-R2 splicing is associated with progression of prostate cancer [1].
• Aberrant fibroblast growth factor receptor 2 signalling in esophageal atresia with tracheoesophageal fistula [2].

High impact information on Fgfr2

• Mutually exclusive splicing of fibroblast growth factor receptor 2 (FGFR2) exons IIIb and IIIc yields two receptor isoforms, FGFR2-IIIb and -IIIc, with distinctly different ligand binding properties [3].
• Alternative splicing of fibroblast growth factor receptor 2 (FGFR2) occurs in a cell-type-specific manner with the mutually exclusive use of exon IIIb or exon IIIc [4].
• An intronic splicing silencer causes skipping of the IIIb exon of fibroblast growth factor receptor 2 through involvement of polypyrimidine tract binding protein [5].
• Loss of expression of a IIIb exon-containing isoform of FGF-R2 [FGF-R2 (IIIb)] accompanies the transition of a well-differentiated, androgen-dependent rat prostate cancer cell line, DT3, to the more aggressive, androgen-independent AT3 cell line [1].
• Fibroblast growth factor receptor 2 (FGFR2) in brain neurons and retinal pigment epithelial cells act via stimulation of neuroendocrine L-type channels (Ca(v)1.3) [6].

Biological context of Fgfr2

• Previously, it has been suggested that IAS2 and a 20-nucleotide core sequence of ISAR form a stem structure that allows for the proper regulation of FGFR2 alternative splicing [4].
• The observed increases in fibroblast growth factor receptor 2 levels may be compensatory to the increased oxidative stress [7].
• Age-related changes in levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2 in the rat inferior colliculus: implications for neural senescence [7].
• Brain-derived neurotrophic factor and fibroblast growth factor 2, and their respective binding sites, tyrosine kinase B receptor and fibroblast growth factor receptor 2, are known to regulate neurite outgrowth and antioxidant enzyme activity [7].
• These observations reveal that homologous FGFR1 and FGFR2 kinases play very different roles in cell growth and differentiation and in development and support of the malignant phenotype [8].

Anatomical context of Fgfr2

• Proliferation of neointimal smooth muscle cells after arterial injury. Dependence on interactions between fibroblast growth factor receptor-2 and fibroblast growth factor-9 [9].
• We have used transfection of rat FGF-R2 minigenes into DT3 and AT3 cancer cell lines to study the mechanisms that control alternative splicing of rat FGF-R2 [1].
• The effectiveness of the fibroblast growth factor receptor 2 response is questionable given the damage that occurs in the inferior colliculus and hippocampus of aged animals [7].
• In contrast, levels of fibroblast growth factor receptor 2 in the inferior colliculus and hippocampus were elevated by approximately 35% in the two older age groups when compared to 3-month-olds [7].
• Rat oligodendrocytes and astrocytes preferentially express fibroblast growth factor receptor-2 and -3 mRNAs [10].

Other interactions of Fgfr2

• This is in addition to the irreversible loss by splice switching of the FGFR2 ectodomain that abrogates response to FGF-7 and homologues from the stroma [8].

Analytical, diagnostic and therapeutic context of Fgfr2

• Immunoprecipitation of FGFR2 led to coprecipitation of alpha 1D Ca(2+) channel subunits and precipitation of alpha 1D subunits led to coprecipitation of FGFR2 [6].
• The signaling cascade of FGFR2 was studied using the perforated patch configuration of the patch-clamp technique in cultured rat retinal pigment epithelial (RPE) cells that express both FGFR1 and FGFR2 [6].

References