Protein tyrosine phosphatase H-type receptor (PTPRH) gene encodes a gastric cancer associated protein, which exerts its biological function through tyrosine phosphorylation in the post-translational COOH- terminal region. PTPRH is abnormally expressed in a variety of tumors, and its biological function is closely related to the occurrence, development and prognosis of tumors.
Humans ; Phosphorylation ; Protein Tyrosine Phosphatases ; Proteins ; Stomach Neoplasms ; Tyrosine

Protein tyrosine phosphatases (PTPs) are key regulatory factors in inflammatory signaling pathways. Although PTPs have been extensively studied, little is known about their role in neuroinflammation. In the present study, we examined the expression of 6 different PTPs (PTP1B, TC-PTP, SHP2, MEG2, LYP, and RPTPβ) and their role in glial activation and neuroinflammation. All PTPs were expressed in brain and glia. The expression of PTP1B, SHP2, and LYP was enhanced in the inflamed brain. The expression of PTP1B, TC-PTP, and LYP was increased after treating microglia cells with lipopolysaccharide (LPS). To examine the role of PTPs in microglial activation and neuroinflammation, we used specific pharmacological inhibitors of PTPs. Inhibition of PTP1B, TC-PTP, SHP2, LYP, and RPTPβ suppressed nitric oxide production in LPS-treated microglial cells in a dose-dependent manner. Furthermore, intracerebroventricular injection of PTP1B, TC-PTP, SHP2, and RPTPβ inhibitors downregulated microglial activation in an LPS-induced neuroinflammation model. Our results indicate that multiple PTPs are involved in regulating microglial activation and neuroinflammation, with different expression patterns and specific functions. Thus, PTP inhibitors can be exploited for therapeutic modulation of microglial activation in neuroinflammatory diseases.
Brain ; Microglia ; Neuroglia ; Nitric Oxide ; Protein Tyrosine Phosphatase, Non-Receptor Type 2 ; Protein Tyrosine Phosphatases*

BACKGROUND: Cytotoxic function of killer cells is inhibited by specific recognition of class I MHC molecules on target cells by inhibitory killer Ig-like receptors (KIR) expressed on NK cells and some cytotoxic T cells. The inhibitory effect of KIR is accomplished by recruitment of SH2-containing protein tyrosine phosphatase (SHP) to the phosphotyrosine residues in the cytoplasmic tail. METHODS: By in vitro coprecipitation experiments and transfection analysis, we investigated the association of KIR with an adaptor protein Shc in Jurkat T cells. RESULTS: The cytoplasmic tail of KIR appeared to associate with an adaptor protein Shc in Jurkat T cell lysates. Similar in vitro experiments showed that phosphorylated KIR cytoplasmic tail bound SHP-1 and Shc in Jurkat T cell lysates. The association of KIR with Shc was further confirmed by transfection analysis in 293T cells. Interestingly, however, Shc appeared to be replaced by SHP-2 upon engagement of KIR in 293T cells. CONCLUSION: Our data indicate that KIR associate with an adaptor protein Shc in Jurkat T cells, and suggest that KIR might have an additional role which is mediated by this adaptor protein.
Cell Proliferation ; Cytoplasm ; Killer Cells, Natural ; Phosphotyrosine ; Protein Tyrosine Phosphatases ; T-Lymphocytes ; Transfection

Oxidative stress plays a critical role in the pathogenesis of asthma. To effectively control oxidative stress in asthmatics, it is important to investigate the precise intracellular mechanism by which the development of immunity, rather than immune tolerance and progression of airway inflammation, is induced. In this article, we suggest that protein tyrosine phosphatases, as intracellular negative regulators, and intracellular antioxidant enzymes such as peroxiredoxins can be regulated by oxidative stress during intracellular signaling.
Antioxidants ; Asthma ; Hypersensitivity ; Immune Tolerance ; Inflammation ; Oxidative Stress ; Peroxiredoxins ; Protein Tyrosine Phosphatases

Reactive oxygen species (ROS) are harmful to cellular components such as proteins, DNA and lipids. The continuous production of ROS during the respiratory electron transfer process has been regarded as the major cause of aging. However, the discoveries of proteins whose structure and function switch with cellular ROS suggest that ROS are active players in cellular regulation. OxyR is the first protein whose ROS-regulated mechanism was revealed by the atomic structure studies. The distantly-located two cysteines in OxyR form a disulfide bond by reaction with ROS, resulting in conformational and functional switches in the protein. The heat shock protein 33 is another protein that is activated by increased level of cellular ROS. Many other cellular proteins including protein tyrosine phosphatases are also regulated by ROS. This review focuses on the structure and function of the ROS-regulated proteins and their implications on the ROS's cellular roles. Detailed studies on the ROS-generating protein machinery and the ROS-regulated proteins should contribute to the therapeutic control of ROS-related diseases and aging processes.
Aging ; DNA ; Electrons ; Heat-Shock Proteins ; Protein Tyrosine Phosphatases ; Proteins ; Reactive Oxygen Species

The phosphorylation and dephosphorylation of proteins on tyrosyl residues are key regulatory mechanisms of cell growth and signal transduction and are controlled by opposing activities of protein tyrosine kinases and phosphotyrosyl phosphatases (PTPs). We have previously cloned and characterized a nontransmembrane chicken protein tyrosine phosphatase 1 (CPTP1) similar to human placental PTP1B (HPTP1B). CPTP1 contains several phosphorylation sequence motifs (S/T-X-X-D/E) for casein kinase II (CKII), [(I > E > V)-Y-(E > G)-(E > D > P > N)-(I/V > L)] for p56(1ck), and (P-E-S-P) for MAP kinase. To examine whether phosphatase activity of CPTP1 could be controlled by phosphorylation, CPTP1 and HPTP1B fusion proteins purified from E. coil were subjected to the in vitro phosphorylation by CKII. Phosphoamino acid analysis revealed that CPTP1 was phosphorylated on both serine and threonine residues by CKII in vitro. In addition, the degree of the phosphorylation of CPTP1 by CKII was shown to be five times higher than that of HPTP1B. Phosphorylation on both serine and threonine residues of CPTP1 in vitro results in an inhibition of its phosphatase activity. This result suggests that phosphorylation of CPTP1 and HPTP1B by CKII might be implicated in the regulation of their catalytic activities in the cell.
Casein Kinase II* ; Casein Kinases* ; Caseins* ; Chickens* ; Clone Cells ; Humans ; Phosphoric Monoester Hydrolases ; Phosphorylation* ; Phosphotransferases ; Protein Tyrosine Phosphatases* ; Protein-Tyrosine Kinases ; Serine ; Signal Transduction ; Threonine

OBJECTIVETo explore the hemolytic mechanism of glucose-6-phosphate dehydrogenase (G6PD) deficient erythrocytes in the view of phosphorylation of membrane protein.

METHODSThe alternation of membrane protein phosphorylation and the effect of dithiothreitol (DTT) on protein phosphorylation were analysed by Western blot technique. The activity of phosphotyrosine phosphatase (PTPs) was determined by using p-nitrophenyl phosphate as substrate.

RESULTSTyrosine phosphorylation of band 3 protein was obviously enhanced in G6PD-deficient erythrocytes. The activity of PTPs was low compared to the normal erythrocytes. The level of phosphotyrosine in G6PD-deficient erythrocytes incubated with DTT was almost the same as in those without DTT. The results were consistent with the activity of PTPs.

CONCLUSIONSPTPs activity reduction and tyrosine phosphorylation enhancement induced by oxidation in G6PD deficiency play an important role in erythrocytes hemolysis. However, the alternation of thiol group is not the only factor affecting the activity of PTPs in G6PD-deficient erythrocytes.

Anion Exchange Protein 1, Erythrocyte ; metabolism ; Blotting, Western ; Erythrocyte Membrane ; metabolism ; Glucosephosphate Dehydrogenase Deficiency ; enzymology ; metabolism ; Humans ; Phosphorylation ; Protein Tyrosine Phosphatases ; metabolism ; Tyrosine ; metabolism

X-linked myotubular myopathy (XLMTM) is a rare congenital muscle disorder, caused by mutations in the MTM1 gene. Affected male infants present severe hypotonia, and generalized muscle weakness, and the disorder is most often complicated by respiratory failure. Herein, we describe a family with 2 infants with XLMTM which was diagnosed by gene analysis and muscle biopsy. In both cases, histological findings of muscle showed severely hypoplastic muscle fibers with centrally placed nuclei. From the family gene analysis, the Arg486STOP mutation in the MTM1 gene was confirmed.
*Codon, Nonsense ; Humans ; Male ; Muscle Hypotonia/genetics/pathology ; Myopathies, Structural, Congenital/*genetics/pathology ; Pedigree ; Protein Tyrosine Phosphatases, Non-Receptor/*genetics

Protein tyrosine phosphatases (PTPs) play an important role in regulating cell signaling events in coordination with tyrosine kinases to control cell proliferation, apoptosis, survival, migration, and invasion. Receptor-type protein tyrosine phosphatases (PTPRs) are a subgroup of PTPs that share a transmembrane domain with resulting similarities in function and target specificity. In this review, we summarize genetic and epigenetic alterations including mutation, deletion, amplification, and promoter methylation of PTPRs in cancer and consider the consequences of PTPR alterations in different types of cancers. We also summarize recent developments using PTPRs as prognostic or predictive biomarkers and/or direct targets. Increased understanding of the role of PTPRs in cancer may provide opportunities to improve therapeutic approaches.
Apoptosis ; Cell Proliferation ; Cell Survival ; Humans ; Neoplasm Invasiveness ; Neoplasms ; enzymology ; Receptor-Like Protein Tyrosine Phosphatases ; genetics ; physiology

PURPOSE: The purpose: of this study was to know the effect of inhibition of protein dephosphorylation on the synthesis of collagen and fibronectin (FN), alkaline phosphatase (ALP) activity, and the formation of bone nodule in MC3T3-E1 osteoblasts using orthovanadate (OVA) which is a potent protein tyrosine phosphatase (PTPases) inhibitor. MATERIALS AND METHODS: The synthesis of collagen, noncollagenous protein (NCP), and percent collagen in MC3T3-E1osteoblasts with or without OVA treatment according to concentration and time sequence was determined by incorporation of [3 H]-proline, synthesis of FN by [35 S] methionine incorproated immunoprecipitation after treatment with 100 M OVA for 24 hours, mRNA expression of collagen and FN by Northern blotting, activity of ALP by spectrophotometric method, and formation of bone nodule by staining method. RESULTS: OVA increased collagen and NCP synthesis concentration dependently, until 12 hours in short-time culture, and time dependently through the differentiation until 29 days, however, there was no significant effect on the percent collagen production. OVA increased percent collagen synthesis significantly at 6 hours, and decreased in a long time culture. Total FN synthesis and FN synthesis in cell layer were increased by OVA, however, FN synthesis in medium was not changed. OVA decreased collagen mRNA level dose-dependently and increased the steady-state level of FN mRNA. OVA inhibited activity of ALP in both short and long-time culture. OVA inhibited bone nodule formation in MC3T3-E1 osteoblasts. CONCLUSION: These results indicate that the inhibition of PTPase by OVA increased the synthesis of collagen, FN, and decreased ALP activity and it resulted in the inhibition of bone formation in MC3T3-E1 osteoblast cells.
Alkaline Phosphatase* ; Blotting, Northern ; Collagen* ; Fibronectins* ; Immunoprecipitation ; Methionine ; Osteoblasts* ; Osteogenesis ; Ovum ; Protein Tyrosine Phosphatases ; RNA, Messenger ; Vanadates*