Genomic organization of the human LAR protein tyrosine phosphatase gene and alternative splicing in the extracellular fibronectin type-III domains.
The structure of the human leukocyte-common antigen-related molecule (LAR) protein tyrosine phosphatase gene was elucidated using phage and cosmid genomic DNA clones. The LAR gene is composed of 33 exons spanning over 85 kilobase pairs. Exon 2 encodes the signal sequence and the first four amino acids in the mature LAR protein. The three immunoglobulin-like domains are encoded by exons 3-7, and the eight fibronectin type III (Fn-III) domains by exons 8-17. Exons 18-22 encode the juxta-membrane and transmembrane domains, and exons 23-33 encode the two conserved tyrosine phosphatase domains and the entire 3'-untranslated region. Exon 1, which presumably encodes the 5'-untranslated sequence, has not been identified. Reverse transcription-polymerase chain reaction analysis revealed the alternative splicing of a mini-exon (exon 13) in the Fn-III domain 5 of human LAR and other related genes (rat LAR, rat PTP sigma, and human PTP delta). RNase protection analysis showed that the human LAR mRNA in which exon 13 is spliced-out is the major mRNA species in all cell lines examined. Reverse transcription-polymerase chain reaction analysis revealed further alternative splicing of LAR mRNA involving the Fn-III domains 4, 5, 6, and 7 in various combinations. These findings will facilitate the understanding of the physiological functions of the LAR extracellular domain.
O'Grady
P
P
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Krueger
N X
NX
Streuli
M
M
Saito
H
H
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000302:isolation & purification; D005091:Exons; D005353:Fibronectins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface
D018076:DNA, Complementary; D005353:Fibronectins; D011956:Receptors, Cell Surface; C516841:PTPRA protein, human; D017027:Protein Tyrosine Phosphatases; C516845:Ptpra protein, rat; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4