A NOVEL FORM OF FGF RECEPTOR-3 USING AN ALTERNATIVE EXON IN THE IMMUNOGLOBULIN DOMAIN-III
A NOVEL FORM OF FGF RECEPTOR-3 USING AN ALTERNATIVE EXON IN THE IMMUNOGLOBULIN DOMAIN-III
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DOI：
10.1016/0014-5793(93)80882-u
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发表时间：
1993-09-20
期刊：
影响因子：
3.5
通讯作者：
GIVOL, D
中科院分区：
文献类型：
--
作者：
AVIVI, A;YAYON, A;GIVOL, D
克隆并鉴定了4种不同的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端一半，c端一半由FGFR1和FGFR2中的外显子IIIb或IIIc编码，而FGFR4缺乏外显子IIIb。外显子IIIb和IIIc的选择性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的外显子IIIa和IIIc之间的基因组序列，并鉴定了另一个外显子，对应于FGFR1和FGFR2的外显子IIIb。该外显子序列显示ig结构域标记，44%与其他FGF受体的外显子IIIb一致，36%与FGFR3的外显子IIIc一致。使用该外显子作为小鼠RNA探针以及PCR分析，证明外显子IIIb编码一种真实形式的FGFR3，该FGFR3在小鼠胚胎、小鼠皮肤和小鼠表皮角质形成细胞中表达。结果表明，ig结构域3外显子的交替存在是FGFR1、2和3的普遍现象，代表了受体多样性产生的一种新的遗传机制。
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.