title: Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences.
abstract: Protein tyrosine phosphatases (PTPases) are a family of enzymes important in cellular regulation. Characterization of two cDNAs encoding intracellular PTPases expressed primarily in hematopoietic tissues and cell lines has revealed proteins that are potential regulators of signal transduction. One of these, SHP (Src homology region 2 [SH2]-domain phosphatase), possesses two tandem SH2 domains at the amino terminus of the molecule. SH2 domains have previously been described in proteins implicated in signal transduction, and SHP may be one of a family of nonreceptor PTPases that can act as direct antagonists to the nonreceptor protein tyrosine kinases. The SH2 domains of SHP preferentially bind a 15,000-Mr protein expressed by LSTRA cells. LSTRA cells were shown to express SHP protein by immunoprecipitation, thus demonstrating a potential physiological interaction. The other PTPase, PEP (proline-, glutamic acid-, serine-, and threonine-rich [PEST]-domain phosphatase), is distinguished by virtue of a large carboxy-terminal domain of approximately 500 amino acids that is rich in PEST residues. PEST sequences are found in proteins that are rapidly degraded. Both proteins have been expressed by in vitro transcription and translation and in bacterial expression systems, and both have been demonstrated to have PTPase activity. These two additional members of the PTPase family accentuate the variety of PTPase structures and indicate the potential diversity of function for intracellular tyrosine phosphatases.
authors.affiliation: Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: R J
authors.initials: RJ
authors.lastname: Matthews
authors.forename: D B
authors.initials: DB
authors.lastname: Bowne
authors.forename: E
authors.initials: E
authors.lastname: Flores
authors.forename: M L
authors.initials: ML
authors.lastname: Thomas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005971:Glutamates; D018698:Glutamic Acid; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006649:Histocompatibility Antigens / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D017493:Leukocyte Common Antigens; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009838:Oligodeoxyribonucleotides; D009928:Organ Specificity; D011392:Proline; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D012694:Serine; D013379:Substrate Specificity; D013912:Threonine
chemical_list: D015703:Antigens, CD; D005971:Glutamates; D006649:Histocompatibility Antigens; D047908:Intracellular Signaling Peptides and Proteins; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D013912:Threonine; D018698:Glutamic Acid; D012694:Serine; D012313:RNA; D004247:DNA; D011392:Proline; D017493:Leukocyte Common Antigens; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases