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 spanni ng over 85 kilobase pairs. Exon 2 encodes the signal sequence and the first four amino acids in the mature LAR protein. The three immunoglob ulin-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 juxtam embrane and transmembrane domains, and exons 23-33 encode the two cons erved tyrosine phosphatase domains and the entire 3'-untranslated regi on. 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, ra t PTP sigma, and human PTP delta). RNase protection analysis showed th at the human LAR mRNA in which exon 13 is spliced out is the major mRN A 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 combinatio ns. These findings will facilitate the understanding of the physiologi cal functions of the LAR extracellular domain.