MOLECULAR CHARACTERIZATION OF THE HUMAN TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASE-DELTA - EVIDENCE FOR TISSUE-SPECIFIC EXPRESSION OF ALTERNATIVE HUMAN TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASE-DELTA ISOFORMS

Protein-tyrosine phosphatases (PTPases) play an essential role in the regulation of cell activation, proliferation, and differentiation. A m ajor subfamily of these enzymes is the transmembrane-type PTPases that contain extracellular regions comprised of Ig-like and fibronectin ty pe III (FN-III)-like domains, Characterization of the human transmembr ane PTPase delta (HPTP delta) revealed the existence of multiple HPTP delta isoforms that vary in their extracellular regions. The full-leng th HPTP delta isoform has an extracellular region containing three Ig- like and eight FN-III-like domains connected via a transmembrane pepti de to an intracellular region with two PTPase domains, whereas another isoform lacks four of the eight FN-III like domains. Furthermore, oth er HPTP delta isoforms exist that lack 9 amino acids within the second Ig-like domain and 4 amino acids at the junction of the second and th ird Ig-like domains or 9 amino acids within the fifth FN-III-like doma in, Reverse transcription polymerase chain reaction analysis demonstra ted that HPTP delta isoforms lacking these short peptides are expresse d in kidney, whereas isoforms containing these peptides are expressed in the brain, Analysis of HPTP delta biosynthesis demonstrated that HP TP delta is expressed as a complex of two noncovalently associated sub units derived from a proprotein and that the HPTP delta ectodomain is shed from the cell surface. Mutational analysis of the HPTP delta prop rotein cleavage site revealed the existence of two or three functional and overlapping furin-like endoprotease cleavage sites.