Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phosphatases (PTPkappa, mu, rho and PCP-2).

Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phosphatases (PTPkappa, mu, rho and PCP-2).
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DOI:
10.1186/1471-2164-5-14
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发表时间:
2004-02-11
期刊:
影响因子:
4.4
通讯作者:
Rotter A
Rotter A
中科院分区:
生物学2区
文献类型:
--
作者:
Besco J;Popesco MC;Davuluri RV;Frostholm A;Rotter A

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R2 B型受体蛋白酪氨酸磷酸酶(RPTPs)由四个基因组成,分别命名为PTP κ(PTPκ)、PTPRL/U(PCP-2)、PTPRM(PTPμ)和PTPRT(PTPρ)。这些跨膜分子与嗜同性细胞粘附有关。在人类中,PTPRL基因位于6号染色体上,PTPRL/U位于1号染色体上,PTPRM位于18号染色体上,PTPRT位于20号染色体上。在小鼠中,四个基因ptprk、ptprl、ptprm和ptprt分别位于染色体10、4、17和2的同线区域。鼠R2 B RPTP基因的基因组组织进行了描述。这四个基因的大小变化很大,从~64 kb到~1 Mb,主要是由于内含子长度的比例差异。虽然也有外显子长度的微小变化,外显子的数量和外显子/内含子交界处的相位是高度保守的。原位杂交地高辛标记的cRNA探针被用来本地化的四个R2 B转录到特定的细胞类型内的小鼠中枢神经系统。全序列的系统发育分析表明,PTPρ和PTPμ的亲缘关系最近,其次是PTPκ。最远的家族成员是PCP-2。RPTP多肽序列的比对预测了假定的可变剪接外显子。PCR实验表明,这些外显子中的五个是选择性剪接的,并且四种磷酸酶中的每一种都以不同的方式将它们整合。最大的变异基因组组织和大多数选择性剪接外显子中观察到的质膜结构域,一个区域的信号转导调控的关键。四个R2 B RPTP基因的比较揭示了几乎相同的基因组组织的原则,尽管基因大小的差异很大,由于内含子长度的变化。虽然也观察到外显子长度的细微差异,但这些基因之间的功能差异可能是由选择性剪接产生的外显子的特定组合引起的。
Four genes designated as PTPRK (PTPκ), PTPRL/U (PCP-2), PTPRM (PTPμ) and PTPRT (PTPρ) code for a subfamily (type R2B) of receptor protein tyrosine phosphatases (RPTPs) uniquely characterized by the presence of an N-terminal MAM domain. These transmembrane molecules have been implicated in homophilic cell adhesion. In the human, the PTPRK gene is located on chromosome 6, PTPRL/U on 1, PTPRM on 18 and PTPRT on 20. In the mouse, the four genes ptprk, ptprl, ptprm and ptprt are located in syntenic regions of chromosomes 10, 4, 17 and 2, respectively. The genomic organization of murine R2B RPTP genes is described. The four genes varied greatly in size ranging from ~64 kb to ~1 Mb, primarily due to proportional differences in intron lengths. Although there were also minor variations in exon length, the number of exons and the phases of exon/intron junctions were highly conserved. In situ hybridization with digoxigenin-labeled cRNA probes was used to localize each of the four R2B transcripts to specific cell types within the murine central nervous system. Phylogenetic analysis of complete sequences indicated that PTPρ and PTPμ were most closely related, followed by PTPκ. The most distant family member was PCP-2. Alignment of RPTP polypeptide sequences predicted putative alternatively spliced exons. PCR experiments revealed that five of these exons were alternatively spliced, and that each of the four phosphatases incorporated them differently. The greatest variability in genomic organization and the majority of alternatively spliced exons were observed in the juxtamembrane domain, a region critical for the regulation of signal transduction. Comparison of the four R2B RPTP genes revealed virtually identical principles of genomic organization, despite great disparities in gene size due to variations in intron length. Although subtle differences in exon length were also observed, it is likely that functional differences among these genes arise from the specific combinations of exons generated by alternative splicing.
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发表时间: 1996-09
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