Chirivi Renato G S, Dilaver Gönül, van de Vorstenbosch Rinske, Wanschers Bas, Schepens Jan, Croes Huib, Fransen Jack, Hendriks Wiljan
Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, University of Nijmegen, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands.
Genes Cells. 2004 Oct;9(10):919-33. doi: 10.1111/j.1365-2443.2004.00773.x.
The use of alternative splice sites, promoters and translation start sites considerably adds to the complexity of organisms. Four mouse cDNAs (PTPBR7, PTP-SL, PTPPBSgamma+ and PTPPBSgamma-) have been cloned that contain different 5' parts but encode identical protein tyrosine phosphatase PTPRR catalytic domains. We investigated the genomic origin and coding potential of these transcripts to elucidate their interrelationship. Mouse gene Ptprr exons were identified within a 260 kbp segment on chromosome 10, revealing PTP-SL- and PTPPBSgamma-specific transcription start sites within introns two and four, respectively, relative to the 14 PTPBR7 exons. Northern and RT-PCR analyses demonstrated differential expression patterns for these promoters. Furthermore, transfection studies and AUG codon mutagenesis demonstrated that in PTP-SL and PTPPBSgamma messengers multiple translation initiation sites are being used. Resulting 72, 60, 42 and 37 kDa PTPRR protein isoforms differ not only in the length of their N-terminal part but also in their subcellular localization, covering all major PTP subtypes; receptor-like, membrane associated and cytosolic. In summary, mouse gene Ptprr gives rise to multiple isoforms through the use of distinct promoters, alternative splicing and differential translation starts. These results set the stage for further investigations on the physiological roles of PTPRR proteins.
可变剪接位点、启动子和翻译起始位点的使用显著增加了生物体的复杂性。已克隆出四个小鼠cDNA（PTPBR7、PTP-SL、PTPPBSgamma+和PTPPBSgamma-），它们含有不同的5'端部分，但编码相同的蛋白酪氨酸磷酸酶PTPRR催化结构域。我们研究了这些转录本的基因组起源和编码潜力，以阐明它们之间的相互关系。在10号染色体上一个260 kbp的片段内鉴定出小鼠基因Ptprr的外显子，相对于14个PTPBR7外显子，分别在第二和第四内含子中揭示了PTP-SL和PTPPBSgamma特异性转录起始位点。Northern和RT-PCR分析表明这些启动子具有不同的表达模式。此外，转染研究和AUG密码子诱变表明，在PTP-SL和PTPPBSgamma信使RNA中使用了多个翻译起始位点。产生的72 kDa、60 kDa、42 kDa和37 kDa的PTPRR蛋白异构体不仅在其N端部分的长度上不同，而且在亚细胞定位上也不同，涵盖了所有主要的PTP亚型；受体样、膜相关和胞质型。总之，小鼠基因Ptprr通过使用不同的启动子、可变剪接和差异翻译起始产生多种异构体。这些结果为进一步研究PTPRR蛋白的生理作用奠定了基础。
