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 major subfamily of these enzymes is the transmembrane-type PTPases that contain extracellular regions comprised of Ig-like and fibronectin type III (FN-III)-like domains. Characterization of the human transmembrane PTPase delta (HPTP delta) revealed the existence of multiple HPTP delta isoforms that vary in their extracellular regions. The full-length HPTP delta isoform has an extracellular region containing three Ig-like and eight FN-III-like domains connected via a transmembrane peptide to an intracellular region with two PTPase domains, whereas another isoform lacks four of the eight FN-III like domains. Furthermore, other 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 third Ig-like domains or 9 amino acids within the fifth FN-III-like domain. Reverse transcription polymerase chain reaction analysis demonstrated that HPTP delta isoforms lacking these short peptides are expressed in kidney, whereas isoforms containing these peptides are expressed in the brain. Analysis of HPTP delta biosynthesis demonstrated that HPTP delta is expressed as a complex of two noncovalently associated subunits derived from a proprotein and that the HPTP delta ectodomain is shed from the cell surface. Mutational analysis of the HPTP delta proprotein cleavage site revealed the existence of two or three functional and overlapping furin-like endoprotease cleavage sites.
Pulido
R
R
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Krueger
N X
NX
Serra-Pagès
C
C
Saito
H
H
Streuli
M
M
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
D018076:DNA, Complementary; D004792:Enzyme Precursors; D007527:Isoenzymes; D012333:RNA, Messenger; D017027:Protein Tyrosine Phosphatases