THE LAR PTP-DELTA/PTP-SIGMA SUBFAMILY OF TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASES - MULTIPLE HUMAN LAR, PTP-DELTA, AND PTP-SIGMA ISOFORMS ARE EXPRESSED IN A TISSUE-SPECIFIC MANNER AND ASSOCIATE WITH THE LAR-INTERACTING PROTEIN LIP.1/

The transmembrane protein-tyrosine-phosphatases (PTPases) LAR, PTP del ta, and PTP sigma each contain two intracellular PTPase domains and an extracellular region consisting of Ig-like and fibronectin type III-l ike domains, We describe the cloning and characterization of human PTP sigma (HPTP sigma) and compare the structure, alternative splicing, t issue distribution, and PTPase activity of LAR, HPTP delta, and HPTP s igma, as well their ability to associate with the intracellular coiled -coil LAR-interacting protein LIP.1. Overall, these three PTPases are structurally very similar, sharing 64% amino acid identity, Multiple i soforms of LAR, HPTP delta, and HPTP sigma appear to be generated by t issue-specific alternative splicing of up to four mini-exon segments t hat encode peptides of 4-16 aa located in both the extracellular and i ntracellular regions. Alternative usage of these peptides varies depen ding on the tissue mRNA analyzed. Short isoforms of both HPTP sigma an d HPTP delta were also detected that contain only four of the eight fi bronectin type III-like domains. Northern blot analysis indicates that LAR and HPTP sigma are broadly distributed whereas HPTP delta express ion is largely restricted to brain, as is the short HPTP sigma isoform containing only four fibronectin type III-like domains, LAR, HPTP del ta, and HPTP sigma exhibit similar in vitro PTPase activities and all three interact with LIP.1, which has been postulated to recruit LAR to focal adhesions, Thus, these closely related PTPases mag perform simi lar functions in various tissues.