FGFR2 异构体剪接
中文名称
通路描述
FGFR2 新生 mRNA 的异构体剪接产生上皮特异性异构体（FGFR2 IIIb）和间质特异性异构体（FGFR2 IIIc）。FGFR2 IIIb 包含外显子 8 或 FGFR2 IIIc 包含外显子 9，改变了受体的 C 末端半部分的 D3 环，并导致两种异构体不同的配体结合特异性。近年来已鉴定出许多顺式和反式作用元件，调控异构体剪接事件。外显子 IIIb 的沉默由外显子两侧存在弱剪接位点、外显子沉默序列（ESS）以及外显子两侧的内含子沉默序列（ISS）介导。hnRNPA1、PTB1、SR 家族蛋白和其他因子与这些元件结合，沉默 IIIb 外显子并促进 FGFR2 IIIc 的表达。在上皮细胞中，上皮特异性因子的招募将剪接事件转向促进外显子 8 的内含。ESPN1 和 ESPN2 是上皮特异性因子，结合内含子 8 中的 ISE/ISS-3 区域以促进 FGFR2 IIIb 特异性剪接。RBFOX2、hnRNPH1 和 hnRNPF 的复合物也通过竞争与 SR 蛋白 ASF/SF2 结合的位点结合，促进上皮特异性剪接，这在间质细胞中起作用。其他蛋白质和序列也被鉴定出来，似乎有助于 FGFR2b 和 FGFR2c 的调控表达，但异构体剪接事件的完整细节尚未完全阐明。
英文描述
FGFR2 alternative splicing Alternative splicing of the FGFR2 nascent mRNA generates an epithelial specific isoform (FGFR2 IIIb) and a mesenchymal specific isoform (FGFR2 IIIc). The inclusion of exon 8 in FGFR2 IIIb or exon 9 in FGFR2 IIIc alters the C-terminal half of the D3 loop of the receptor and is responsible for the different ligand-binding specificities of the two isoforms (reviewed in Eswarakumar et al, 2005). In recent years, a number of cis- and trans-acting elements have been identified that regulate the alternative splicing event. Exon IIIb repression is mediated by the presence of weak splice sites flanking the exon, an exonic silencing sequence (ESS) within the IIIb exon and both intronic silencing sequences (ISS) upstream and downstream (Carstens et al, 2000; Del Gatto and Breathnach, 1995; Del Gatto et al, 1996; Wagner et al 2005; Wagner and Garcia-Blanco, 2001). Binding of hnRNPA1, PTB1, SR family proteins and other factors to these elements represses the IIIb exon and promotes FGFR2 IIIc expression in mesenchymal cells (Del Gatto-Konczak et al, 1999; Carstens et al, 2000; Wagner et al, 2005; Wagner and Garcia-Blanco, 2001; Wagner and Garcia-Blanco, 2002). In epithelial cells, recruitment of epithelial specific factors shifts the splicing events to favour inclusion of exon 8. ESPN1 and ESPN2 are epithelial-specific factors that bind to an ISE/ISS-3 (intronic splicing enhancer/intronic splicing silencer-3) region within intron 8 to promote FGFR2 IIIb-specific splicing (Warzecha et al, 2009). A complex of RBFOX2, hnRNPH1 and hnRNPF also contribute to epithelial-specific splicing by competing for binding to a site that is occupied by the SR proteins ASF/SF2 in mesenchymal cells (Baraniak et al, 2006; Mauger et al, 2008). Other proteins and sequences have also been identified that appear to contribute to the regulated expression of FGFR2b and FGFR2c, but the full details of the alternative splicing event remain to be worked out (Muh et al, 2002; Newman et al, 2006; Del Gatto et al, 2000; Hovhannisyan and Carstens, 2007).
所含基因
26 个基因