A novel protein-tyrosine phosphatase with homology to both the cytoskeletal proteins of the band 4.1 family and junction-associated guanylate kinases.
Reversible phosphorylation of proteins on tyrosine residues is critical in several cellular activities. The removal of the phosphate groups from tyrosine-phosphorylated proteins is accomplished by a class of enzymes which constitute a large family of related proteins, the protein tyrosine phosphatases. We report here the isolation of a complementary DNA encoding a novel protein tyrosine phosphatase, which we termed hPTP1E. Several overlapping cDNA clones were isolated to reconstruct a sequence of 8301 nucleotides. Northern blot analysis of poly(A)+ RNA from different human tissues revealed the presence of a mRNA of 8.2-8.5 kilobases suggesting the near full-length sequence had been cloned. The composite hPTP1E cDNA contains an open reading frame encoding 2490 amino acid residues. The predicted protein (M(r) = 277,567) does not contain a signal peptide or a membrane-spanning region and possesses a single catalytic domain (amino acids 2241-2470). The recombinant phosphatase domain has been expressed in Escherichia coli, purified to near homogeneity and showed to possess specific protein tyrosine phosphatase activity. The primary structure of hPTP1E also displays homology to cytoskeleton- and membrane junction-associated proteins. Thus, the region encompassing amino acids 568-1053 is related to the cytoskeletal proteins of the band 4.1 family. In addition, hPTP1E contains five imperfect repeats possessing significant homology to the GLGF repeats of the junction-associated guanylate kinases such as the Drosophila discs-large tumor suppressor gene (dlg-1). The structural features of hPTP1E suggest that it localizes at the junction between the plasma membrane and the cytoskeleton where it may regulate signal transduction and cytoskeletal integrity.
Banville
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D
Sector of Pharmaceutical Biotechnology, National Research Council of Canada, Montreal, Québec.
Ahmad
S
S
Stocco
R
R
Shen
S H
SH
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003598:Cytoskeletal Proteins / Q000235:genetics*; D018076:DNA, Complementary; D004910:Erythrocyte Membrane / Q000378:metabolism; D004926:Escherichia coli; D017629:Gap Junctions / Q000201:enzymology; D051528:Guanylate Kinases; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009479:Neuropeptides; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics*; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification; D014407:Tumor Cells, Cultured
D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases