Rinske van de Vorstenbosch

PubMed2006

Proteolytic processing of the receptor-type protein tyrosine phosphatase PTPBR7.

The single-copy mouse gene Ptprr gives rise to different protein tyrosine phosphatase (PTP) isoforms in neuronal cells through the use of distinct promoters, alternative splicing, and multiple translation initiation sites. Here, we examined the array of post-translational modifications imposed on the PTPRR protein isoforms PTPBR7, PTP-SL, PTPPBSgamma42 and PTPPBSgamma37, which have distinct N-terminal segments and localize to different parts of the cell. All isoforms were found to be short-lived, constitutively phosphorylated proteins. In addition, the transmembrane isoform, PTPBR7, was subject to N-terminal proteolytic processing, in between amino acid position 136 and 137, resulting in an additional, 65-kDa transmembrane PTPRR isoform. Unlike for some other receptor-type PTPs, the proteolytically produced N-terminal ectodomain does not remain associated with this PTPRR-65. Shedding of PTPBR7-derived polypeptides at the cell surface further adds to the molecular complexity of PTPRR biology.

Animals↗

PubMed2004

Characterization of multiple transcripts and isoforms derived from the mouse protein tyrosine phosphatase gene Ptprr.

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.

Alternative Splicing↗