Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The PTP-2 cDNA encoding an intracellular protein tyrosine phosphatase (PTPase-2) was isolated and sequenced from mouse testis and T-cell cDNA libraries. This PTP-2 cDNA was found to be homologous to human PTP-TC and rat PTP-S, and contained 1,551 nucleotides, including 1,146 nucleotides encoding 382 amino acids as well as 5' (61 nucleotides) and 3' (344 nucleotides) non-coding regions. Northern blot analysis indicated that PTP-2 mRNA of 1.9 Kb was most abundant in testis and kidney, although it was also present in spleen, muscle, liver, heart and brain.
Mol Cell Biochem 1992 Dec 02
PMID:Molecular cloning, nucleotide sequence and expression of a cDNA encoding an intracellular protein tyrosine phosphatase, PTPase-2, from mouse testis and T-cells. 128 99

The importance of parasite-directed phosphatases in such diseases as smallpox and the bubonic plague emphasizes the need to understand the molecular events associated with the normal function of protein tyrosine phosphatase in eukaryotic cells.
Mol Microbiol 1991 Nov
PMID:Microbial pathogenesis and tyrosine dephosphorylation: surprising 'bedfellows'. 172 71

Protein tyrosine phosphorylation has been implicated in the growth and functional responses of hematopoietic cells. Recently, approaches have been developed to characterize the protein tyrosine phosphatases that may contribute to regulation of protein tyrosine phosphorylation. One novel protein tyrosine phosphatase was expressed predominantly in hematopoietic cells. Hematopoietic cell phosphatase encodes a 68-kDa protein that contains a single phosphatase conserved domain. Unlike other known protein tyrosine phosphatases, hematopoietic cell phosphatase contains two src homology 2 domains. We also cloned the human homolog, which has 95% amino acid sequence identity. Both the murine and human gene products have tyrosine-specific phosphatase activity, and both are expressed predominantly in hematopoietic cells. Importantly, the human gene maps to chromosome 12 region p12-p13. This region is associated with rearrangements in approximately 10% of cases of acute lymphocytic leukemia in children.
Mol Cell Biol 1992 Feb
PMID:Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13. 173 48

Homogeneous preparations of a protein phosphatase that is specific for phosphotyrosyl residues (protein tyrosine phosphatase [PTPase] 1B) were isolated from human placenta and microinjected into Xenopus oocytes. This resulted in an increase in activity of up to 10-fold over control levels, as measured in homogenates with use of an artificial substrate (reduced carboxamidomethylated and maleylated lysozyme). Microinjected PTPase was stable for at least 18 h. It is distributed within the oocyte in a manner similar to the endogenous activity and is suggestive of an interaction with cellular structures or molecules located predominantly in the animal hemisphere. The phosphatase markedly retarded (by up to 5 h) maturation induced by insulin. This, in conjunction with the demonstration that PTPase 1B abolished insulin stimulation of an S6 peptide (RRLSSLRA) kinase concomitant with a decrease in the phosphorylation of tyrosyl residues in a protein with the same apparent Mr as the beta subunit of the insulin and insulinlike growth factor 1 receptors (M. F. Cicirelli, N. K. Tonks, C. D. Diltz, E. H. Fischer, and E. G. Krebs, submitted for publication), provides further support for an essential role of protein tyrosine phosphorylation in insulin action. Furthermore, maturation was significantly retarded even when the PTPase was injected 2 to 4 h after exposure of the cells to insulin. PTPase 1B also retarded maturation induced by progesterone and maturation-promoting factor, which presumably do not act through the insulin receptor. These data point to a second site of action of the PTPase in the pathway of meiotic cell division, downstream of the insulin receptor and following the appearance of active maturation-promoting factor.
Mol Cell Biol 1990 Feb
PMID:Effect of microinjection of a low-Mr human placenta protein tyrosine phosphatase on induction of meiotic cell division in Xenopus oocytes. 215 16

A recent report indicated that T200 molecules interact with elements of the cytoskeleton in BW5147 T lymphoma cells. We have confirmed the cytoskeletal association of T200 by examining nonionic detergent-soluble and detergent-insoluble fractions of murine T cell tumor cell lines, cloned cytotoxic T lymphocyte lines, and thymocytes. Concanavalin A (Con A)-treated and untreated cells were extracted with 0.5% Triton X-100 and the remaining insoluble material was extracted under conditions allowing actin depolymerization. In the absence of Con A treatment, little T200 could be recovered from the depolymerized insoluble fraction. However, in T cells treated with capping concentrations of Con A, a considerable amount of T200 was rendered insoluble in nonionic detergent, and T200 could be recovered from the insoluble fraction by a buffer which dissociates actin polymers. A lesser, but still significant, amount of T200 associated with the detergent-insoluble fraction of thymocytes treated with concentrations of Con A and succinyl Con A, which are mitogenic for T cells. We also found that in T cells treated with mitogenic concentrations of succinyl Con A, more T200 associated with cytoskeleton than did H-2 or LFA-1 molecules. Because T200 is such a predominant molecule on the surface of T cells, such translocations of the molecule may have a major impact on the physiology of the cell, especially if T200 functions as a protein tyrosine phosphatase as recent evidence by others suggests.
Mol Immunol 1989 Oct
PMID:Concanavalin A induces a cytoskeletal association of T200 molecules in T lymphocytes. 253 40

A brain-enriched protein tyrosine phosphatase termed STEP46 (striatal enriched phosphatase) was previously isolated and characterized. Immunological studies with a STEP monoclonal antibody recognized several STEP-immunoreactive proteins, and suggested that additional STEP-related polypeptides existed. This study reports the isolation of two alternatively spliced transcripts of the STEP gene. One of these, STEP20 (with a predicted molecular mass of 20 kDa) was further characterized and found to lack the conserved tyrosine phosphatase domain. Northern analysis detected a 2.8 kb STEP20 message in mouse brain. The second alternatively spliced transcript, STEP61, has a 5'-extended open reading frame that encodes a protein with a predicted molecular mass of 61 kDa and contains a single tyrosine phosphatase domain. The exon-intron organization responsible for the novel STEP20 and STEP61 sequences was determined in the mouse STEP genomic DNA. We propose that the original STEP46, along with STEP20 and STEP61, are members of a brain-enriched subfamily of protein tyrosine phosphatases, and that STEP isoforms may have distinct functions within the central nervous system.
Brain Res Mol Brain Res 1995 Aug
PMID:Identification of two alternatively spliced transcripts of STEP: a subfamily of brain-enriched protein tyrosine phosphatases. 749 67

PEP is an intracellular protein tyrosine phosphatase expressed primarily by cells of hematopoietic origin that can be divided structurally into a catalytic domain and a large carboxy-terminal domain. The carboxy-terminal domain is enriched in proline, glutamic acid, serine, and threonine residues (PEST sequences) and contains a nonperfect tandem repeat sequence enriched in proline residues and a carboxy terminus enriched in basic amino acids. Here we show that PEP is diffusely expressed in lymphoid tissues, consistent with expression by many different cell types. Analysis of the PEP protein identifies a nuclear localization sequence within the extreme carboxy terminus. Transfer of 18 amino acids from the carboxy terminus of PEP to beta-galactosidase conferred nuclear localization, indicating that this sequence was sufficient for nuclear localization. Proteins enriched in PEST sequences are often rapidly degraded. However, pulse-chase analysis indicates that PEP has a half-life of greater than 5 h.
Mol Cell Biol 1994 Jul
PMID:Nuclear localization of the PEP protein tyrosine phosphatase. 751 75

The nuclear mechanism by which GH acts to induce gene expression after binding to its receptor on the cell surface is not defined. We have characterized an element in the 5'-flanking region of the rat GH-responsive serine protease inhibitor (Spi) 2.1 gene responsible for its induction by GH. This element binds a hepatic nuclear protein(s) in a GH state-specific manner. Activation of binding by GH does not require de novo protein synthesis, suggesting that a reversible posttranslational process is required for binding to the element. To define the mechanism of this process, hepatic nuclear extracts were analyzed by electrophoretic mobility shift assays using a DNA fragment (-147 to -103) of the Spi 2.1 gene. Treatment of extracts with phosphatases resulted in a marked reduction of GH state-specific binding. Addition of phosphatase inhibitors antagonized the reduction in binding after phosphatase treatment. The specific nature of the phosphorylation event involved in binding was explored using phosphotyrosine antibodies and a protein tyrosine phosphatase. Treatment of nuclear extracts with either of these reagents ablated binding to the response element. Because the tyrosine-phosphorylated transcription factor protein p91 has recently been implicated in cytokine signal transduction mediated by JAK2, we sought evidence that p91 was part of the GH-responsive binding complex. Analysis of an enriched preparation of GH-inducible binding complexes by Western blots using anti-p91 demonstrated no immunoreactivity. We conclude that tyrosine phosphorylation of a nuclear factor is required for GH state-specific binding to this GH response element in vivo, but that p91 is not present in the binding complex.
Mol Endocrinol 1994 Dec
PMID:Binding of a growth hormone-inducible nuclear factor is mediated by tyrosine phosphorylation. 753 94

Its reactivity to the antiphosphotyrosine 4G10 monoclonal antibody by Western blot analysis demonstrated that the human estrogen receptor (hER) from human MCF-7 cells and the recombinant hER expressed in Sf9 insect cells were phosphorylated on tyrosine(s). Reverse phase-HPLC separation of a tryptic digest of the 32P-labeled purified hER from Sf9 and MCF-7 cells followed by amino acid and radiolabel sequencing revealed that tyrosine-537 was phosphorylated. The phosphorylation on tyrosine-537 was independent of estradiol treatment of MCF-7 cells, indicating that tyrosine-537 is a basal phosphorylation site. Two src family tyrosine kinases, p60c-src and p56lck, phosphorylated the purified recombinant hER on tyrosine-537 in vitro. In addition, two tyrosine phosphatases, protein tyrosine phosphatase-1B and src homology-2 protein tyrosine phosphatase-1, dephosphorylated phosphotyrosine-537 of the hER in vitro. These data suggest that tyrosine phosphorylation of the hER is regulated by potentially oncogenic tyrosine kinases and phosphatases that may modulate the function of ER in normal and/or abnormal cell growth.
Mol Endocrinol 1995 Jan
PMID:Phosphorylation of the human estrogen receptor on tyrosine 537 in vivo and by src family tyrosine kinases in vitro. 753 6

The role of persistent protein phosphorylation upon gonadotropin releasing hormone (GnRH) stimulated luteinizing hormone (LH) release was investigated by the use of the selective inhibitors of protein phosphatase type 1 (PP1) and 2A (PP2A), okadaic acid (OA) and calyculin A. Pre-incubation of cultured rat pituitary cells with OA (24 h) or calyculin A (30 min) resulted in inhibition of GnRH-stimulated LH release with significant inhibition being detected at 10 nM and 30 nM for OA and calyculin A, respectively. The inactive OA analog norokadone and the protein tyrosine phosphatase inhibitor vanadyl hydroperoxide had no significant effect on GnRH-induced LH release. The stimulatory effects of the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol 13-acetate (TPA, 50 ng/ml) or the Ca2+ ionophore, ionomycin (1 micron), upon LH release were also abolished by pretreatment with OA (10-20 nM) or calyculin A (30 nM). Stimulation of LH release by high K+ (28 mM) or residual LH release stimulated by GnRH in Ca(2+)-free medium were also blocked by OA. These observations indicate that protein dephosphorylation is involved positively in GnRH-stimulated LH release. The site of action of the protein phosphatases PP1 and PP2A is most likely downstream to Ca2+ elevation and PKC activation by GnRH.
Mol Cell Endocrinol 1995 Apr 28
PMID:Involvement of protein phosphatases in gonadotropin releasing hormone regulated gonadotropin secretion. 764 55


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