Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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protein tyrosine phosphatase, non-receptor type 6(PTPN6) protein tyrosine phosphatase, non-receptor type 6(PTPN6) Related Genes Homo sapiens
CHROMOSOME 12,
CYTOBAND 12p13,
ENSEMBL_GENE_ID ENSG00000111679,
GENERIF_SUMMARY The Lyn/CD22/SHP-1 pathway is important in autoimmunity. Naive and tolerant B-cells differ in their calcium signaling in response to antigenic stimulation., peripheral blood monocytes treated for 5--8 days with GM-CSF (i.e. mature Mphi) acquired the capacity to assemble tyrosine phosphatase SHP-1 with CD9, alpha3-beta1 integrin and their CD46., SHP-1 is recruited to the NK cell immune synapse within 1 min in both cytolytic and noncytolytic conjugates, allowing clear distinction between noncytolytic and cytolytic interactions at this early time., interacts with siglec-11, evidence of cytokine-regulated SHP-1 nuclear localization mediated by a bipartite nuclear localization signal, suggesting that SHP-1 regulates nuclear signaling in cell growth control., ILT2 triggering on cutaneous T-cell lymphoma (CTCL) cells leads to the recruitment of SHP-1 and to the specific inhibition of CTCL malignant cell proliferation in Sezary syndrome induced by CD3/T-cell receptor. (TCR) stimulation., In the T cell line HUT-78, JAK3 was found to be highly phosphorylated. These results suggest that SHP-1 might be involved in maintaining the IL-2R/JAK3 signaling pathway under control and point towards a role of SHP-1 in the pathogenesis of the disease., Functional loss of SHP1 is associated with the pathogenesis of leukemias/lymphomas., participation in regulation of Stat6 dephosphorylation, crystal structure of the C-terminal truncated human SHP-1 in the inactive conformation at 2.8-A resolution and refined the structure to a crystallographic R-factor of 24.0%, SHP-1 may be involved in the regulation of beta-catenin transcriptional function and in the negative control of intestinal epithelial cell proliferation, show the existence of multiple transcripts of SHP-1 in human transformed T cells and normal PBMCs and give evidence supporting the concept that SHP-1 can negatively regulate growth of malignant T cells, SHP-1 plays a pivotal role in reorganization of cytoskeletal architecture by inducing actin dephosphorylation., A blockade in early signaling events observed with TCR antagonists occurs via a negative intracellular signal that is mediated by SHP-1., Associates with phosphorylated Fc gamma RIIa to modulate signaling events in myeloid cells, Vav1 trapping was independent of actin polymerization, suggesting that inhibition of cellular cytotoxicity occurs through an early dephosphorylation of Vav1 by SHP-1, which blocks actin-dependent activation signals., SHP-1 inhibits PRL receptor and EPO receptor signaling by recruitment and targeting of SOCS-1 to Jak2, highlighting a new mechanism of SHP-1 regulation of cytokine-receptor signaling., Down-regulation of SHP1 is associated with adult T-cell leukemia, SHP1 gene silencing is one of the events critical to the onset of malignant lymphomas/leukemias in humans., hypermethylated in multiple myeloma, SHP-1 can dephosphorylate alpha-actinin in vitro and in vivo., CNS myelination was significantly reduced in SHP-1-deficient mice relative to their normal littermates at multiple times during the active period of myelination., Mice lacking SHIP-1 have defects in the erythroid and myeloid compartments similar to those in mice lacking Lyn or SHP-1., inactivation of Ros by SHP-1-mediated dephosphorylation plays a role in the regulation of complex stability, TFG is a novel protein able to modulate SHP-1 activity., transformation of TF-1 cells with FLT3/ITD mutations suppressed the activity of SHP-1 by approximately 3-fold, SHP-1 may be a novel target molecule to sensitize erythropoietin action in hemodialysis patients with hyporesponsive anemia, SHP-1 acts at multiple stages of hematopoietic differentiation to alter lineage balance. Expression of WT SHP-1 reduced myeloid colony numbers while increasing the numbers of secondary embryoid bodies and mixed hematopoietic colonies obtained, SRIF inhibitory effects on thyroid medullary carcinoma cell proliferation are mediated, at least in part, by SHP-1, which acts through a MAPK-dependent mechanism, STAT3 may transform cells by inducing epigenetic silencing of SHP-1 in cooperation with DNMT1 and histone deacetylase 1, Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2, Our results suggest an alteration of the SHP-1 modulation by GM-CSF in lipid rafts of PMN with aging. These alterations could contribute to the decreased GM-CSF effects on PMN., SHP1 activation, association with Src and dephosphorylation of specific proteins were dependent on extracellular calcium and maintenance of a higher cytosolic calcium plateau., Protein phosphatase 6 specifically down-regulates transforming growth factor beta-activated kinase 1 (TAK1) through dephosphorylation of threonine-187 in the activation loop, suppressing inflammatory responses via TAK1 signaling pathways., increased activity of inhibitory molecules, such as Src homology domain-containing protein tyrosine phosphatase-1 (SHP-1) and suppressors of cytokine signalling (SOCS), is responsible for age-related failure of GM-CSF to stimulate neutrophil functions, findings provide an insight into the structure of the hematopoietic cell-specific P2 promoter of the SHP-1 gene and identify PU.1 as the transcriptional activator of the P2 promoter, These data suggest a mechanism of IC-mediated inhibition of IFN-gamma signaling, which requires the ITAM-containing FcgammaRI, as well as the ITIM-dependent phosphatase SHP-1, ultimately resulting in the suppression of STAT1 phosphorylation., SHP-1 loss correlates with, and may contribute to, progression of cutaneous T-cell lymphoma, novel mechanism regulating GH signaling in which estrogen receptor modulators enhance GH activation of the JAK2/STAT5 pathway in a cell-type-dependent manner by attenuating protein tyrosine phosphatase activities, In human erythrocytes SHP-1 is present in membranes from resting cells, but in 5% of the protein amount. SHP-1 ensures band 3 dephosphorylation., SHP-1 and SHP-2, two structurally related cytoplasmic protein-tyrosine phosphatases with different cellular functions and cell-specific expression patterns, were compared for their intrinsic susceptibility to oxidation by H(2)O(2)., A novel 6-mer motif SKHKED within the carboxyl terminus of SHP-1 is necessary and sufficient for lipid raft localization and for the function of SHP-1 as a negative regulator of T-cell receptor signaling., Thus the phosphorylation and dephosphorylation of caspase-8, mediated by Lyn and SHP-1, respectively, represents a novel, dynamic post-translational mechanism for the regulation of neutrophil apoptosis, Mononuclear leukocytes of multiple sclerosis patients have a deficiency in SHP-1 and increased inflammatory gene expression., SHP-1 plays an important role in regulating oxidative stress., TIMP1 functions as a differentiating and survival factor of GC B cells by modulating CD44 and SHP1 in the late centrocyte/post-GC stage, regardless of EBV infection., Our results demonstrate putative roles of SHP-1 and SHP-2 in the progression of both Condyloma acuminatum and cervical cancer after HPV infection., in HTLV-1-transformed CD4+ T cells, TIPS causes dissociation of transcription factors from the core SHP-1 P2 promoter, which in turn leads to subsequent DNA methylation, an important early step for leukemogenesis., IL-10 suppresses the co-stimulatory effect of CD2 in T cells that have intact SHP-1, demonstrating an essential role of SHP-1 in IL-10-mediated direct T cell suppression., Downregulation of platelet responsiveness upon contact with LDL by the protein-tyrosine phosphatases SHP-1 and SHP-2., Leishmania can exploit a host protein tyrosine phosphatase, namely SHP-1, to directly inactivate IRAK-1., Deletion of the SHP-1 gene by small interfering RNA abolished the ability of boswellic acid to inhibit STAT3 activation., The kinetic and mechanistic details of reversible oxidation of SHP-1 and SHP-2, were investigated., Lyn is downstream of Jak2, and Jak2 maintains activated Lyn kinase in CML through the SET-PP2A-Shp1 pathway., 5-aza-2'-deoxycytidine can re-express the silent SHP-1 gene, inhibit cell proliferation and induce apoptosis in K562 cells., macrophages of multiple sclerosis patients display a deficiency of SHP-1 expression, heightened activation of STAT6, STAT1, and NF-kappaB and a corresponding inflammatory profile, Data suggest that age-specific interactions between Siglec-9 and SHP-1 may influence the altered inflammatory responsiveness and longevity of neonatal polymorphonuclear neutrophils., increased frequency of promoter hypermethylation in SHP1 gene in acute myeloid leukemia compared to chronic myeloid leukemia., Demethylation in HT-29 cells recovered the constitutive expression of SOCS-1 and SHP-1., The SHP-1, As(2)O(3) could cause demethylation and re-expression of SHP-1 in T2 lymphoma cells, and may inhibit proliferation and induce apoptosis., p53 repression of SHP-1 expression leads to trkA-Y674/Y675 phosphorylation and trkA-dependent suppression of breast-cancer cell proliferation., SHP-1 is phosphorylated in a dynamic fashion after endorepellin stimulation. It is an essential mediator of endorepellin activity. A novel functional interaction between the integrin alpha2 subunit & SHP-1 is described., Data show that SHP-1 knockdown increases p27stability, decreases the CDK6 levels, inducing retinoblastoma protein hypophosphorylation, downregulation of cyclin E and thereby a decrease in the CDK2 activity., SHP-1 plays a minor role in determining autoimmune hemolytic anemia and its expression is upregulated in monocytes from these patients., As2O3 can effectively cause demethylation and inhibit the growth of tumor by reactivating the SHP-1 gene transcription., Plumbagin inhibits STAT3 activation pathway through the induction of SHP-1 and this may mediate the sensitization of STAT3 overexpressing cancers to chemotherapeutic agents., SHP-1 plays an important role in airway mucin production through regulating oxidative stress., Forced expression of SOCS3 and SHP-1 inhibits IFN-alpha signaling in psoriatic T cells., 5-aza-dc can induce SHP1 expression and inhibit JAK2/STAT3/STAT5 signalling, TonEBP/OREBP is extensively regulated by phosphatases, including SHP-1, whose inhibition by high NaCl increases phosphorylation of TonEBP/OREBP at Y143, contributing to the nuclear localization and activation of TonEBP/OREBP, These results suggest that calpain-dependent cleavage of SHP-1 and SHP-2 may contribute to protein tyrosine dephosphorylation in Jurkat T cell death induced by Entamoeba histolytica., Results support the notion that the tumor suppressor effects of SHP1 on NPM-ALK are dependent on its ability to bind to this oncogenic protein., SHP-1 may be a therapeutic target in prostate cancer, even when there is an IL-6-related growth advantage., SHP-1 has disparate effects on subpopulations of responding CD8 T lymphocytes, reducing the number of short-lived effector cells generated without affecting the size of the memory precursor effector cell pool that leads to long-term memory formation., SHP-1 negatively controls tyrosine phosphorylation of beta-catenin, thus inhibiting its association with TATA-binding protein and promotes beta-catenin degradation into the proteasome through a GSK3beta-dependent mechanism., REVIEW, Transgenic SHP-1 inhibits signaling through multiple receptors and regulates NF-kappaB and transcription factor activator protein (AP)-1 signaling in dendritic cells., an alteration in PTPN6/SHP1 may contribute to neutrophilic dermatoses, Crystal structure of human protein tyrosine phosphatase SHP-1 in the open conformation, Immunoreceptor-tyrosine-based-activation-motifs suppressive signals subvert the activating function of rafts to promote incorporation of receptors into supramolecular domains where signaling molecules are deactivated by SHP-1., Inhibitory ITAM signaling traps activating receptors with the phosphatase SHP-1 to form polarized "inhibisome" clusters., Data indicate that CD300F is an active regulator of TLR-mediated macrophage activation through association with SHP-1 involving MyD88 and/or TRIF., SHP-1 is expressed significantly higher in multisystem than single-system Langerhans cell histiocytosis, in serum- or IGF-1-stimulated breast cancer MCF-7 cells, JNK induces SHP1 expression through the binding of AP-4 and RFX-1 transcription factors to the epithelial tissue-specific SHP1 promoter., SHP-1 antagonizes the action of receptor and non-receptor-tyrosine kinases on GIV and down-regulates the phospho-GIV-PI3K-Akt axis of signaling., impaired signaling is associated with enhanced phagocytosis in neonatal monocyte-derived macrophages, data demonstrate that constitutive activation of STAT3 in Sezary syndrome is not due to the loss of SHP-1, but is mediated by constitutive aberrant activation of JAK family members, SHP-1 could be a new biologic indicator at baseline of IMA sensitivity in patients with chronic myelogenous leukemia., These findings showed a novel role for SHP-1 in the regulation of Akt activity through the modulation of the ghrelin/GHSR1a system signaling, Methylation at the SHP-1 promoter in plasma is associated with non-small cell lung cancer., regulation of the TLR3/TRIF-mediated pathway required the combined action of SHP-1 and SHP-2, which could be accomplished by CD300f but not CD300a., Data show that silencing of SHP-1 by RNA interference abolished the effects of dovitinib on p-STAT3, indicating that SHP-1, a protein tyrosine phosphatase, mediates the effects of dovitinib., Data show that that SPL/RGS/SHP1 complexes are present in resting platelets where constitutive phosphorylation of SPL(Y398) creates an atypical binding site for SHP-1., it is indicated that the SHP-1 methylation plays important role in the pathogenesis of myelodysplastic syndrome via activating the JAK/STAT pathway probably, SHP-1 plays a critical role in abrogating M. pneumoniae-induced IL-8 production in nonasthmatic airway epithelial cells through inhibition of PI3K/Akt and NF-kappaB activity, but it is defective in asthma., Studies indicate that CD45, nonreceptor SH2 domain-containing PTP-1 (SHP-1) and PEST domain-enriched tyrosine phosphatase (PEP) are expressed at elevated levels in immune cells and play essential roles in T cell homeostasis., Increased SHP-1 promoter methylation may relate in part to decreased SHP-1 expression and increased leukocyte-mediated inflammation in multiple sclerosis., PTPN6 epigenetic silencing was recurrent in primary effusion lymphoma & diffuse large B-cell lymphoma, with a higher prevalence in the non-germinal centre subtype. It was associated with the activation of the Jak-Stat pathway., Mice lacking protein tyrosine phosphatase Shp1 specifically in dendritic cells (DCs) develop splenomegaly associated with more CD11c+ DCs., LST1 is expressed specifically in leukocytes of the myeloid lineage, where it localizes to the tetraspanin-enriched microdomains and it binds SHP-1 and SHP-2 phosphatases., Abnormal methylation of SHP-1 gene promoter might have tentative role in the pathogenesis and progression of myelodysplastic syndrome., IFN-beta and IFN-gamma/TNF-alpha decrease erythrophagocytosis by human monocytes in vitro, and this effect does not apparently require an increase in SIRP-alpha or SHP-1 expression., Data suggest that protein tyrosine phosphatase non-receptor type 6 (SHP-1) may interact with EGF receptor (EGFR) to inhibit proliferation., This study is the first to identify and define an interaction between SHP-1 and an SH3 domain-containing protein. Our findings provide an alternative way that SHP-1 can be linked to potential substrates., Data show that TIMP-2-mediated inhibition of vascular endothelial cell permeability involves an integrin alpha3beta1-Shp-1-cAMP/protein kinase A-dependent vascular endothelial cadherin cytoskeletal association., The global role of SHP-1 in regulating CD8 positive T cell activation., These results suggest the involvement of the ZAP70 and PTPN6 genes in the genetic component conferring a general susceptibility to Crohn's disease and ulcerative colitis, respectively., Data suggest growth retardation in idiopathic short stature is related to delayed activation of JAK2 (Janus kinase 2) by PTP1B (protein tyrosine phosphatase, non-receptor type 1) and SHP1 in response to GH/GHR (growth hormone/GH receptor) signaling., The endothelial tyrosine phosphatase SHP-1 plays an important role for vascular hemostasis in vivo, which is crucial in TNF alpha -induced endothelial inflammation., A high level of SHP1P2 methylation of hilar lymph nodes from stage I NSCLC patients is associated with early relapse of disease., SHP1 decreases the radiosensitivity of non-small cell lung cancer cells through affecting cell cycle distribution, results strongly suggest that expression of NTRK1-pY674/pY675 together with wild-type TP53 and low levels of PTPN6 expression are predictors of improved disease-free survival in breast cancer, studies have uncovered novel epigenetic mechanisms of PTPN6 suppression and suggest that PTPN6 may be a potential target of epigenetic therapy in DLBCL., study identified novel SHP-1 transcripts in epithelial cancer cells; each product of ORF SHP-1 transcripts has phosphatase activity and isoforms with an N-SH2 deletion have increased phosphatase activity and novel protein-protein interactions; study documents utilization of promoter 2 by SHP-1 transcripts and a noncoding transcript in epithelial cells, PTPN6 expression may be a factor contributing to poor survival for anaplastic glioma patients., hERG and hEAG channels are regulated by Src and by SHP-1 tyrosine phosphatase via an ITIM region in the cyclic nucleotide binding domain., decreased expression levels of SHP-1 caused by aberrant promoter hypermethylation may play a key role in the progression of CML by dysregulating BCR-ABL1, AKT, MAPK, MYC and JAK2/STAT5 signaling., SHP-1 expression ws lower in PBMCs from unmedicated schizophrenics. The promoter region was hypermethylated. Silencing SHP-1 induced IKK/NF-kB and pro-inflammatory cytokines. SHP-1 expression may explain 30% of the clinical negative symptom variance., We demonstrated that the association and oxidation of c-Src and SHP-1 by ROS are key steps in enhancing OC survival, which are responsible for increased bone loss when ovarian function ceases., A PKC-SHP1 signaling axis desensitizes Fcgamma receptor signaling by reducing the tyrosine phosphorylation of CBL and regulates FcgammaR mediated phagocytosis., transcription factor RFX-1 regulates SC-2001-mediated SHP-1 Phosphatase transcription in hepatocellular carcinoma cells., SHP-1 is a potent suppressor of epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma., SHP-1(I) presented concordance between unmethylated promoter region and tumor for breast or prostate., Results show that dissociation of SHP-1 from spinophilin is followed by an increase in the binding of spinophilin to PP1., Data show that SHP-1 promotes HIF-1alpha degradation under hypoxic conditions leading to a reduction in VEGF synthesis and secretion and impairing epithelial cells proliferation., Inactivation of SHP1 is associated with myeloproliferative neoplasm., Soluble egg antigens glycans are essential for induction of enhanced SOCS1 and SHP1 levels in dendritic cells via the mannose receptor., Phosphorylation of ATR and CHK1 did not show significant differences in the three cell groups. Overexpression of SHP-1 in the CNE-2 cells led to radioresistance and the radioresistance was related to enhanced DNA DSB repair., miR-4649-3p is downregulated in nasopharyngeal carcinoma cell lines accompanied with SHP-1 upregulation., SHP-1 has a critical role in radioresistance, cell cycle progression, and senescence of nasopharyngeal carcinoma cells, MiR-378g enhanced radiosensitivity partially by targeting SHP-1 in NPC cells., Data demonstrate for the first time that SHP1 methylation has high specificity for diagnosis of endometrial carcinoma, while CDH13 promoter methylation plays a role in the earlier stage., A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo which reduces tumor size and prolonged survival time., In addition to their role in NK cell activation by hematopoietic cells, the SLAM-SAP-SHP1 pathways influence responsiveness toward nonhematopoietic targets by a process akin to NK cell 'education'.,
SP_COMMENT catalytic activity:Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate., function:Plays a key role in hematopoiesis. This PTPase activity may directly link growth factor receptors and other signaling proteins through protein-tyrosine phosphorylation. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation., PTM:Phosphorylated on serine and tyrosine residues., similarity:Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily., similarity:Contains 1 tyrosine-protein phosphatase domain., similarity:Contains 2 SH2 domains., subcellular location:In neurons, translocates into the nucleus after treatment with angiotensin II., subunit:Monomer. Interacts with MTUS1 (By similarity). Binds PTPNS1, LILRB1 and LILRB2. Interacts with FCRL2, FCRL3, FCRL4, CD300LF and CD84., tissue specificity:Isoform 1 is expressed in hematopoietic cells while isoform 2 is expressed in non-hematopoietic cells.,