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Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, University of Nijmegen, Geert Grooteplein 28, 6525 GA Nijmegen, the Netherlands
The use of alternative splice sites, promoters and translation start sites considerably adds to the complexity of organisms. Four mouse cDNAs (PTPBR7, PTP-SL, PTPPBS
+ and PTPPBS
) 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 PTPPBS
-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 PTPPBS
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.
R. G. S. Chirivi and G. Dilaver contributed equally to this work.
* Correspondence: E-mail: w.hendriks{at}ncmls.kun.nl
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