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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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Classification of receptor-like protein tyrosine phosphatases (RPTPs) into eight subfamilies (R1-R8), based on sequence similarity among PTP catalytic domains [3]. PTPμ, κ, ρ and PCP-2 are members of the R2B subfamily.
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Figure 1: Classification of receptor-like protein tyrosine phosphatases (RPTPs) into eight subfamilies (R1-R8), based on sequence similarity among PTP catalytic domains [3]. PTPμ, κ, ρ and PCP-2 are members of the R2B subfamily.

Mentions: RPTPs have been divided into eight major subfamilies (Figure 1), based on phylogenetic analysis of the phosphatase domains [3]. Four of these subfamilies (R2A, R2B, R3, and R4) play critical roles in CNS development [4]. Common to all Type 2 RPTPs is an extracellular segment containing a combination of multiple fibronectin and immunoglobulin (Ig)-like domains, and a single transmembrane region. The intracellular region contains a membrane proximal juxtamembrane domain, followed by a catalytically active tyrosine phosphatase domain and a second inactive domain. Type 2 RPTPs have been further subdivided into two distinct classes (R2A and R2B). Genes in the R2B class are differentiated from the R2A class by an additional MAM (Meprin/ A5/PTP mu) domain at the N-terminus [5]. In addition to a putative role in signal transduction, R2B molecules have cell adhesive properties [6]. Because no invertebrate homologues of the four R2B molecules have been found to date [7], and no ESTs indicative of R2Bs have been isolated from invertebrates, the function(s) of these phosphatases is likely to be highly specific to vertebrate species.


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)

Classification of receptor-like protein tyrosine phosphatases (RPTPs) into eight subfamilies (R1-R8), based on sequence similarity among PTP catalytic domains [3]. PTPμ, κ, ρ and PCP-2 are members of the R2B subfamily.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Classification of receptor-like protein tyrosine phosphatases (RPTPs) into eight subfamilies (R1-R8), based on sequence similarity among PTP catalytic domains [3]. PTPμ, κ, ρ and PCP-2 are members of the R2B subfamily.
Mentions: RPTPs have been divided into eight major subfamilies (Figure 1), based on phylogenetic analysis of the phosphatase domains [3]. Four of these subfamilies (R2A, R2B, R3, and R4) play critical roles in CNS development [4]. Common to all Type 2 RPTPs is an extracellular segment containing a combination of multiple fibronectin and immunoglobulin (Ig)-like domains, and a single transmembrane region. The intracellular region contains a membrane proximal juxtamembrane domain, followed by a catalytically active tyrosine phosphatase domain and a second inactive domain. Type 2 RPTPs have been further subdivided into two distinct classes (R2A and R2B). Genes in the R2B class are differentiated from the R2A class by an additional MAM (Meprin/ A5/PTP mu) domain at the N-terminus [5]. In addition to a putative role in signal transduction, R2B molecules have cell adhesive properties [6]. Because no invertebrate homologues of the four R2B molecules have been found to date [7], and no ESTs indicative of R2Bs have been isolated from invertebrates, the function(s) of these phosphatases is likely to be highly specific to vertebrate species.

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