Avivi A, Yayon A, Givol D
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
FEBS Lett. 1993 Sep 20;330(3):249-52. doi: 10.1016/0014-5793(93)80882-u.
Four distinct FGF receptors were cloned and characterized and it was demonstrated that the ligand binding site of FGF receptors is confined to the extracellular immunoglobulin-like (Ig)-domain 2 and 3. The Ig-domain 3 is encoded by two separate exons: exon IIIa encodes the N-terminal half, and the C-terminal half is encoded by either exon IIIb or IIIc in FGFR1 and FGFR2, whereas FGFR4 is devoid of exon IIIb. Alternative usage of exons IIIb and IIIc determine the ligand binding specificity of the receptor. To analyze the arrangement of these exons in FGFR3 we cloned the genomic sequence between exon IIIa and IIIc of FGFR3 and identified an alternative exon, corresponding to exon IIIb of the FGFR1 and FGFR2. The sequence of this exon shows Ig-domain hallmarks, 44% identity with exon IIIb of other FGF receptors and 36% identity with exon IIIc of FGFR3. Using this exon as a probe for mouse RNA as well as PCR analysis, demonstrated that exon IIIb encodes an authentic form of FGFR3 that is expressed in mouse embryo, mouse skin and mouse epidermal keratinocytes. The results demonstrate that the presence of alternative exons for Ig-domain 3 is a general phenomena in FGFR1, 2 and 3, and represents a novel genetic mechanism for the generation of receptor diversity.
克隆并鉴定了四种不同的成纤维细胞生长因子（FGF）受体，结果表明FGF受体的配体结合位点局限于细胞外免疫球蛋白样（Ig）结构域2和3。Ig结构域3由两个独立的外显子编码：外显子IIIa编码N端的一半，而在FGFR1和FGFR2中，C端的一半由外显子IIIb或IIIc编码，而FGFR4没有外显子IIIb。外显子IIIb和IIIc的交替使用决定了受体的配体结合特异性。为了分析这些外显子在FGFR3中的排列，我们克隆了FGFR3外显子IIIa和IIIc之间的基因组序列，并鉴定出一个与FGFR1和FGFR2的外显子IIIb相对应的可变外显子。该外显子的序列显示出Ig结构域的特征，与其他FGF受体的外显子IIIb有44%的同一性，与FGFR3的外显子IIIc有36%的同一性。使用该外显子作为小鼠RNA的探针以及PCR分析表明，外显子IIIb编码一种在小鼠胚胎、小鼠皮肤和小鼠表皮角质形成细胞中表达的真实形式的FGFR3。结果表明，Ig结构域3可变外显子的存在是FGFR1、2和3中的普遍现象，并且代表了一种产生受体多样性的新遗传机制。
