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

Besco J, Popesco MC, Davuluri RV, Frostholm A, Rotter A - BMC Genomics (2004)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, The Ohio State University, Columbus, Ohio 43210, USA. besco.1@osu.edu

ABSTRACT

Background: Four genes designated as PTPRK (PTPkappa), PTPRL/U (PCP-2), PTPRM (PTPmu) and PTPRT (PTPrho) 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.

Results: The genomic organization of murine R2B RPTP genes is described. The four genes varied greatly in size ranging from approximately 64 kb to approximately 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 PTPrho and PTPmu were most closely related, followed by PTPkappa. 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.

Conclusions: 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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Murine R2B phylogenetic relationships. Parsimony tree constructed from full-length sequences of mouse R2B cDNAs. PTPρ and PTPμ are most closely related.
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Figure 10: Murine R2B phylogenetic relationships. Parsimony tree constructed from full-length sequences of mouse R2B cDNAs. PTPρ and PTPμ are most closely related.

Mentions: The phylogenetic relationship of the entire sequence of the R2B phosphatases encompassing both extra- and intracellular regions was compared. Analysis of the full-length mouse cDNA nucleotide and predicted amino acid sequences indicated that the four genes originated from a common ancestor that gave rise to two separate branches (Figure 10). Of the four R2B genes, PTPρ (ptprt) and PTPμ (ptprm) were most closely related, followed by PTPκ (ptprk). The most distant member was PCP-2 (ptprl). Previous phylogenetic analyses, based solely on the comparison of the first [3,24] and second [25] phosphatase domains, provided similar results. A priori, the four type R2B phosphatases could have arisen either by a single fusion event followed by at least two rounds of duplication, or by several separate fusion events. In the first instance, the phylogenetic tree generated by comparing the first phosphatase domains should be the same as that generated by comparing the entire proteins. Different phylogenetic trees would be expected if the four R2B phosphatases were generated by separate fusion events. Our finding that the phylogenetic relationship of the four complete proteins is the same as that of the phosphatase domains argues in favor of the former explanation, and supports the contention that during the transition from single-celled to multicellular organisms, double domain phosphatases originated by duplication, followed by fusion to cell adhesion-like genes [25].


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

Besco J, Popesco MC, Davuluri RV, Frostholm A, Rotter A - BMC Genomics (2004)

Murine R2B phylogenetic relationships. Parsimony tree constructed from full-length sequences of mouse R2B cDNAs. PTPρ and PTPμ are most closely related.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC373446&req=5

Figure 10: Murine R2B phylogenetic relationships. Parsimony tree constructed from full-length sequences of mouse R2B cDNAs. PTPρ and PTPμ are most closely related.
Mentions: The phylogenetic relationship of the entire sequence of the R2B phosphatases encompassing both extra- and intracellular regions was compared. Analysis of the full-length mouse cDNA nucleotide and predicted amino acid sequences indicated that the four genes originated from a common ancestor that gave rise to two separate branches (Figure 10). Of the four R2B genes, PTPρ (ptprt) and PTPμ (ptprm) were most closely related, followed by PTPκ (ptprk). The most distant member was PCP-2 (ptprl). Previous phylogenetic analyses, based solely on the comparison of the first [3,24] and second [25] phosphatase domains, provided similar results. A priori, the four type R2B phosphatases could have arisen either by a single fusion event followed by at least two rounds of duplication, or by several separate fusion events. In the first instance, the phylogenetic tree generated by comparing the first phosphatase domains should be the same as that generated by comparing the entire proteins. Different phylogenetic trees would be expected if the four R2B phosphatases were generated by separate fusion events. Our finding that the phylogenetic relationship of the four complete proteins is the same as that of the phosphatase domains argues in favor of the former explanation, and supports the contention that during the transition from single-celled to multicellular organisms, double domain phosphatases originated by duplication, followed by fusion to cell adhesion-like genes [25].

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, The Ohio State University, Columbus, Ohio 43210, USA. besco.1@osu.edu

ABSTRACT

Background: Four genes designated as PTPRK (PTPkappa), PTPRL/U (PCP-2), PTPRM (PTPmu) and PTPRT (PTPrho) 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.

Results: The genomic organization of murine R2B RPTP genes is described. The four genes varied greatly in size ranging from approximately 64 kb to approximately 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 PTPrho and PTPmu were most closely related, followed by PTPkappa. 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus