Affinage

PTPN6

Tyrosine-protein phosphatase non-receptor type 6 · UniProt P29350

Length
595 aa
Mass
67.6 kDa
Annotated
2026-06-10
100 papers in source corpus 47 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTPN6/SHP-1 is a cytoplasmic non-receptor protein tyrosine phosphatase that functions as a central negative regulator of immune receptor, cytokine, growth factor, and integrin signaling, with loss of expression causing the severe hematopoietic and autoimmune phenotype of motheaten mice (PMID:8324828, PMID:8638162). Its activity is governed by an autoinhibitory mechanism in which the N-SH2 domain occludes the catalytic active site (crystal structure), and engagement of the SH2 domains shifts the enzyme to an open, active conformation that exposes the catalytic pocket (PMID:12482860, PMID:21465528). Activation is achieved physiologically through recruitment to phosphotyrosine-bearing ITIM receptors such as LAIR-1, FCRL5, and FcγRIII, and through phosphorylation: Lyn phosphorylates Tyr536/Tyr564 to enable maximal activity and Stat5 interaction, while PKD phosphorylates Ser557 to promote TCR signaling during positive selection; its activity is additionally subject to reversible redox inactivation by H2O2 (PMID:11160222, PMID:17522256, PMID:22415018, PMID:20858858, PMID:27670070, PMID:9739453). SHP-1 has narrow substrate specificity favoring acidic and aromatic residues flanking the phosphotyrosine (PMID:21291263, PMID:10660565). Once active it dephosphorylates a broad set of substrates to dampen signaling, including ZAP-70 and LAT in TCR signaling, JAK2 and STAT3 in cytokine pathways, p85-PI3K, Cbl-b, CBL, p62(DOK), TrkA, TRPV1, α-actinin, and CEACAM1, thereby setting activation thresholds and controlling apoptosis, phagocytosis, integrin adhesion, and insulin sensitivity (PMID:8638162, PMID:11420038, PMID:9814969, PMID:10545526, PMID:10488096, PMID:26416283, PMID:12176909, PMID:14662744, PMID:25790452, PMID:15070900, PMID:16617349). In neutrophils SHP-1 also restrains p38 MAPK-driven cytokine production and maintains Ripk1 function to prevent inflammatory cell death (PMID:31819256). Through suppression of JAK/STAT, NF-κB, and AKT signaling, SHP-1 acts as a tumor suppressor in hepatocellular carcinoma and modulates leukemia stem cell metabolism and immune evasion (PMID:29776962, PMID:38321204).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1993 High

    Established the causal link between PTPN6/SHP-1 loss and disease by showing that motheaten mutations disrupt the gene and abolish phosphatase expression, defining SHP-1 as essential for normal hematopoiesis.

    Evidence DNA sequencing, Western blot, and activity assays on motheaten (me/mev) mouse genomic clones

    PMID:8324828

    Open questions at the time
    • Did not define molecular substrates
    • Did not establish the biochemical mechanism of regulation
  2. 1996 High

    Defined SHP-1 as a negative regulator of antigen receptor signaling by demonstrating it binds and dephosphorylates ZAP-70 to raise the TCR activation threshold.

    Evidence Co-IP, kinase activity assays, and dominant-negative SHP-1 expression in T cells

    PMID:8638162

    Open questions at the time
    • Did not address upstream receptors recruiting SHP-1
    • Mechanism of activation unresolved
  3. 1997 High

    Showed SHP-1 acts within distinct inhibitory coreceptor pathways and can also positively regulate Src, revealing context-dependent positive and negative roles.

    Evidence SHP-1/SHIP-deficient B cell lines and apoptosis assays; in vitro Src dephosphorylation in motheaten thymocytes

    PMID:9242674 PMID:9244303 PMID:9261115

    Open questions at the time
    • Did not reconcile how the same enzyme can be inhibitory or activating in different contexts
    • Substrate selection determinants unknown
  4. 1998 Medium

    Identified cytokine-pathway substrates and a redox switch, showing SHP-1 terminates JAK2/STAT signaling and is reversibly inactivated by oxidation.

    Evidence Neutralizing antibody electroporation and JAK2 co-IP/activity assays; in vitro H2O2 inactivation and reducing-agent reactivation

    PMID:9739453 PMID:9814969

    Open questions at the time
    • JAK2 finding from single lab with limited orthogonal validation
    • Physiological relevance of redox regulation in vivo not established
  5. 1999 High

    Expanded the substrate repertoire to PI3K signaling, apoptosis, and growth control by identifying p85-PI3K, p62(DOK), and JAK2/STAT3 as targets and demonstrating membrane recruitment is required for apoptosis.

    Evidence Co-IP, catalytically inactive mutants, PI3K activity and apoptosis assays; motheaten macrophages; POMC reporter in AtT-20 cells

    PMID:10488096 PMID:10506221 PMID:10545526 PMID:10585470 PMID:9740804

    Open questions at the time
    • Direct versus indirect dephosphorylation not always distinguished
    • Spatial regulation of recruitment incompletely defined
  6. 2000 High

    Provided the first atomic-level view of substrate recognition and added p120 catenin as a substrate, defining the structural basis of specificity.

    Evidence X-ray crystallography of the catalytic domain with SIRPα peptides; GST pulldown, co-IP and MS for p120 catenin

    PMID:10660565 PMID:10835420

    Open questions at the time
    • Full-length autoinhibition mechanism not yet visualized
    • p120 catenin functional consequence single-lab
  7. 2001 High

    Linked receptor recruitment to substrate dephosphorylation by showing ITIM receptor LAIR-1 binds and activates SHP-1, and raft-targeted SHP-1 selectively dephosphorylates LAT.

    Evidence Yeast tri-hybrid, membrane co-IP and activity assays; chimeric raft-targeting SHP-1 in Jurkat cells

    PMID:11160222 PMID:11420038

    Open questions at the time
    • How substrate selectivity (LAT vs ZAP-70) is achieved spatially not fully resolved
  8. 2002 High

    Defined the master regulatory mechanism: the N-SH2 domain autoinhibits the active site, and death-receptor phosphotyrosine motifs recruit SHP-1 to control survival.

    Evidence X-ray crystallography of truncated SHP-1; phosphomotif mapping, co-IP and Lyn kinase assay in neutrophils

    PMID:11786908 PMID:12482860

    Open questions at the time
    • The active open conformation was not yet structurally captured
    • Conformational transition kinetics unknown
  9. 2003 High

    Extended SHP-1 function into neuronal apoptosis and tumor suppression, identifying TrkA as a substrate and proteasomal JAK degradation as a downstream consequence.

    Evidence Co-IP with phosphosite mapping and motheaten mice for TrkA; SHP-1 transfection with MG132 for JAK degradation

    PMID:14624462 PMID:14662744

    Open questions at the time
    • JAK degradation study lower mechanistic depth (Medium)
    • Direct versus indirect routes to JAK turnover unclear
  10. 2004 High

    Demonstrated a cytoskeletal substrate by purifying SHP-1 as the α-actinin phosphatase, broadening its role into structural protein regulation.

    Evidence Chromatographic purification, MS identification, in vitro dephosphorylation, COS-7 co-transfection with catalytic mutant

    PMID:15070900

    Open questions at the time
    • Physiological setting of α-actinin dephosphorylation not defined in vivo
  11. 2006 High

    Established SHP-1 as a metabolic and inflammatory regulator, controlling insulin receptor/CEACAM1 signaling and macrophage antimicrobial responses.

    Evidence Viable motheaten mice with dominant-negative adenovirus and shRNA; insulin clearance and signaling assays; motheaten macrophage NO suppression by Leishmania

    PMID:16617349 PMID:17057094

    Open questions at the time
    • Tissue-specific contributions to insulin sensitivity not fully dissected
    • Pathogen-driven SHP-1 activation mechanism incompletely defined
  12. 2007 High

    Connected SHP-1 to transcriptional control of its own expression and to additional ITIM receptors, mapping how SHP-1 abundance and recruitment are governed.

    Evidence Reporter, EMSA, ChIP and siRNA for PU.1; FCRL5-ITIM mutational analysis and calcium assays

    PMID:17218319 PMID:17522256

    Open questions at the time
    • Other transcriptional regulators of PTPN6 not addressed
  13. 2010 High

    Resolved an activation mechanism by showing Lyn-mediated Tyr536/Tyr564 phosphorylation is required for maximal activity and Stat5 suppression, preventing myeloproliferative disease.

    Evidence Lyn/PLC-β3 knockout mice, Y536F/Y564F mutants, activity and Stat5 assays

    PMID:20858858

    Open questions at the time
    • Interplay between tyrosine phosphorylation and SH2-mediated activation not fully integrated
  14. 2011 High

    Quantified intrinsic substrate specificity and captured the open active conformation, completing the structural model of conformational activation.

    Evidence Combinatorial peptide library kinetics; X-ray crystallography of full-length open SHP-1

    PMID:21291263 PMID:21465528

    Open questions at the time
    • How specific receptors trigger the autoinhibited-to-open transition in cells not directly shown
  15. 2012 High

    Demonstrated direct roles in phagosome maturation and revealed inhibitory signaling through the classic activating receptor FcγRIII.

    Evidence Confocal microscopy and phagosome fractionation in motheaten macrophages; intravital microscopy and FcγRIII/FcγRIIB-deficient mice

    PMID:22415018 PMID:22826316

    Open questions at the time
    • Substrates mediating phagolysosome biogenesis not identified
    • Mechanism of FcγRIII-SHP-1 coupling incompletely defined
  16. 2013 High

    Defined SHP-1 as a negative regulator of STAT3-driven Th17 differentiation, linking it to adaptive immune polarization.

    Evidence T cell-specific knockout, dominant-negative transgenic, pharmacologic inhibition, Th17 and STAT3 assays

    PMID:22438258

    Open questions at the time
    • Direct STAT3 dephosphorylation versus upstream effects in this context not fully separated
  17. 2015 High

    Added Cbl-b, TRPV1, and STAT3 as substrates across immune, sensory, and cancer contexts, and showed the open/catalytic mutant directly dephosphorylates STAT3.

    Evidence Co-IP and Shp1-/- mice for Cbl-b; patch clamp and in vivo inhibition for TRPV1; D61A/C453S mutants in HCC EMT assays

    PMID:25619838 PMID:25790452 PMID:26416283

    Open questions at the time
    • In vivo substrate selectivity determinants across tissues not resolved
  18. 2016 High

    Identified a positive regulatory phosphorylation by PKD at Ser557 required for TCR-driven thymocyte development, broadening SHP-1 regulation beyond tyrosine phosphorylation.

    Evidence PKD2/PKD3 double-deficient mice, phosphoproteomics, S557A knock-in, T cell development analysis

    PMID:27670070

    Open questions at the time
    • How Ser557 phosphorylation alters conformation or activity mechanistically not defined
  19. 2018 High

    Revealed positive (signal-promoting) roles for SHP-1 in TGF-β receptor signaling and HSC quiescence, and confirmed tumor-suppressor function in hepatocarcinogenesis.

    Evidence Shp-1 knockout mice and TGFβR1 co-IP for HSC quiescence; conditional hepatocyte Ptpn6 knockout with DEN and orthotopic HCC models

    PMID:29669741 PMID:29776962

    Open questions at the time
    • Mechanistic basis for SHP-1 promoting rather than dampening TGF-β signaling not resolved
  20. 2019 High

    Established that neutrophil SHP-1 restrains p38 MAPK cytokine production and maintains Ripk1 to prevent programmed cell death, explaining the inflammatory motheaten phenotype.

    Evidence Conditional neutrophil Ptpn6 deletion with Ripk1/Ripk3/Mlkl/caspase-8 epistasis crosses and cytokine assays

    PMID:31819256

    Open questions at the time
    • Direct SHP-1 substrates within the Ripk1/cell-death axis not identified
  21. 2020 Medium

    Connected SHP-1 to checkpoint and innate signaling, mediating PD-L1 suppression of TRPV1 nociception and linking it to TRAF6/STING-dependent inflammation.

    Evidence Conditional NaV1.8+ neuron knockout with electrophysiology and pain behavior; co-IP of SHP-1 with TRAF6/NLRX1 in ischemia models

    PMID:32151250 PMID:32960817

    Open questions at the time
    • TRAF6/DJ-1 finding is Medium-confidence with limited catalytic evidence
    • Whether SHP-1 acts catalytically or as a scaffold in STING/TRAF6 contexts unclear
  22. 2022 Medium

    Implicated SHP-1 in TLR4/innate immune adaptor complexes and STING regulation, suggesting scaffold-associated functions beyond classical phosphatase activity.

    Evidence Co-IP of SKAP2-Sirpα-SHP-1 complex and SKAP2 knockout mice; co-IP and ubiquitination assays for SHP-1-STING with pharmacological epistasis

    PMID:35034964 PMID:36273174

    Open questions at the time
    • Limited direct SHP-1 enzymatic evidence in these contexts
    • Single-lab findings awaiting independent confirmation
  23. 2023 High

    Identified podocin SUMOylation regulation as a non-canonical SHP-1 function protecting against diabetic kidney disease.

    Evidence Podocyte-specific Ptpn6 knockout, MS SUMOylation analysis, glomerular phenotyping

    PMID:37507049

    Open questions at the time
    • Mechanistic link between SHP-1 phosphatase activity and SUMO2 modification of podocin not fully defined
  24. 2024 High

    Defined a metabolic and immune-evasion axis whereby SHP-1 inhibition reprograms leukemia stem cell glycolysis via AKT-β-catenin-PFKP and promotes MYC degradation.

    Evidence SHP-1 inhibition in LSCs, pathway and metabolic assays, MYC degradation analysis, in vivo AML models

    PMID:38321204

    Open questions at the time
    • Direct SHP-1 substrate upstream of the AKT-β-catenin axis not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single phosphatase achieves context-specific selection among its many substrates and switches between negative and positive regulatory roles in different cells remains unresolved.
  • No unified model linking receptor recruitment, phosphorylation state, and substrate choice
  • Scaffold versus catalytic contributions in innate immune complexes not separated
  • Determinants of positive (TGF-β, Src) versus negative regulation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 12 GO:0098772 molecular function regulator activity 6 GO:0016787 hydrolase activity 5 GO:0005198 structural molecule activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1430728 Metabolism 2
Partners
CBLCBL-BJAK2LAIR-1STAT3TRKATRPV1ZAP-70

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The motheaten (me) and viable motheaten (mev) mutations in mice are point mutations within the Hcph (PTPN6/SHP-1) gene that cause aberrant splicing, resulting in deficient SHP-1 protein expression and activity, and severe hematopoietic defects. Western blot, activity assays, cDNA molecular analysis, DNA sequencing of genomic clones Cell High 8324828
1996 SHP-1 binds directly to the protein tyrosine kinase ZAP-70 upon T cell activation; this interaction increases SHP-1 phosphatase activity and decreases ZAP-70 kinase activity, establishing SHP-1 as a negative regulator that sets the threshold of TCR activation. Co-immunoprecipitation, kinase activity assays, dominant-negative SHP-1 expression in T cells Science High 8638162
1997 SHP-1 preferentially dephosphorylates Src at its carboxyl-terminal inhibitory phosphotyrosine site, activating Src kinase; Src associates with SHP-1 and phosphorylates SHP-1 via the NH2-terminal SH2 domain interaction, demonstrating a positive regulatory role of SHP-1 on Src activity. In vitro dephosphorylation assay, co-immunoprecipitation, kinase activity assays in SHP-1-deficient motheaten thymocytes, dominant-negative SHP-1 expression The Journal of biological chemistry High 9261115
1997 SHP-1 and SHIP define two distinct inhibitory signaling pathways downstream of inhibitory coreceptors: FcγRIIB-class inhibitory signaling requires SHIP and not SHP-1, whereas KIR-class inhibitory signaling requires SHP-1 and not SHIP. SHP-1-mediated inhibitory signaling blocks BCR-triggered apoptosis. Generation of SHP-1- or SHIP-deficient B cell lines, functional inhibitory signaling assays, apoptosis assays Cell High 9244303
1997 SHP-1 is dispensable for FcγRIIB-mediated inhibition of B cell antigen receptor (sIgM) signaling; SHIP is recruited to tyrosyl-phosphorylated FcγRIIB and mediates inhibition in the absence of SHP-1. Immortalized SHP-1-deficient (me/me) B cell lines, calcium influx assays, co-immunoprecipitation of SHIP The Journal of biological chemistry High 9242674
1998 SHP-1 is responsible for JAK2 dephosphorylation and termination of angiotensin II-induced JAK/STAT cascade in vascular smooth muscle cells, while SHP-2 has an opposing role in initiating JAK2 phosphorylation; SHP-1 forms complexes with JAK2. Electroporation with neutralizing antibodies, time-course co-immunoprecipitation, JAK2 kinase activity assays The American journal of physiology Medium 9814969
1998 SHP-1 phosphatase activity is reversibly inactivated by oxidation (H2O2); activity can be restored by dithiothreitol, glutathione, or N-acetylcysteine, establishing redox regulation as a mechanism controlling SHP-1 activity. In vitro H2O2 inactivation assay, reactivation with reducing agents, H2O2-stimulated SHP-1-transfected HeLa cells Biochemistry and molecular biology international Medium 9739453
1999 SHP-1 co-immunoprecipitates with the p85 regulatory subunit of PI3K in T cells; this association increases upon TCR ligation and requires Lck-phosphorylated Tyr564 on SHP-1. Wild-type SHP-1 (but not catalytically inactive mutant) dephosphorylates p85 and reduces PI3K activity and downstream Akt phosphorylation. Co-immunoprecipitation, co-expression with constitutively active Lck in COS7 cells, PI3K enzyme activity assay, phospho-Akt Western blot The Journal of biological chemistry High 10488096
1999 SHP-1 is constitutively associated with JAK2 in pituitary AtT-20 cells; LIF induces recruitment of phosphorylated STAT3 to this SHP-1/JAK2 complex. SHP-1 dephosphorylates JAK2 and STAT3 to attenuate LIF-induced POMC promoter activity, as shown by wild-type vs. dominant-negative SHP-1 overexpression. Co-immunoprecipitation, dominant-negative and wild-type SHP-1 overexpression, POMC luciferase reporter, phospho-JAK2/STAT3 Western blot The Journal of clinical investigation High 10545526
1999 Membrane-associated SHP-1 is required for receptor-mediated intracellular acidification and apoptosis in breast cancer cells (initiated by somatostatin receptor activation and Fas ligation); catalytically inactive SHP-1 (C455S) acts as dominant negative, blocking recruitment of wild-type SHP-1 to the membrane and preventing apoptosis. Ectopic SHP-1 expression, catalytically inactive mutant (C455S), SST agonist and Fas ligation assays, pH measurement, apoptosis assays The Journal of biological chemistry Medium 10506221
1999 SHP-1 dephosphorylates and associates with p62(DOK) in macrophages; p62(DOK) is constitutively associated with SHP-1 and is constitutively hyperphosphorylated in SHP-1-deficient (motheaten) macrophages, correlating with growth factor-independent survival. Co-immunoprecipitation, Far Western analysis, comparison of wild-type vs. me/me motheaten macrophages, SHP-1 C453S catalytically inactive mutant The Journal of biological chemistry High 10585470
2000 Crystal structure of the SHP-1 catalytic domain complexed with SIRPα-derived peptide substrates reveals that the variable β5-loop-β6 motif confers substrate specificity at P-4 and further N-terminal subpockets, and identifies a novel residue shift at P-2. X-ray crystallography of catalytic domain–peptide substrate complexes The Journal of biological chemistry High 10660565
2000 SHP-1 binds to and dephosphorylates p120 catenin (3A isoform) in EGF-stimulated cells; binding is mediated primarily by the N-terminal SH2 domain of SHP-1; tetracycline-mediated decrease of SHP-1 expression elevates p120 catenin phosphorylation. GST-SHP-1 pulldown, co-immunoprecipitation, mass spectrometry identification of p120ctn, tetracycline-regulated SHP-1 expression The Journal of biological chemistry Medium 10835420
2000 SHP-1 deficiency in macrophages leads to enhanced αmβ2 integrin-mediated adhesion/spreading and a 10–15-fold increase in D-3 phospholipid products of PI3-kinase, with 2–5-fold increased membrane-associated PI3-kinase activity; PI3-kinase inhibitors cause detachment, placing SHP-1 upstream of PI3-kinase in integrin adhesion regulation. Comparison of mev/mev vs. wild-type macrophages, PI3-kinase activity and lipid product assays, PI3-kinase inhibitors (wortmannin, LY294002) Current biology High 9740804
2001 SHP-1 is constitutively associated with and activated by the ITIM-containing receptor LAIR-1 at the plasma membrane in resting human T cells (both Jurkat and primary), as identified by yeast tri-hybrid screen and confirmed by co-immunoprecipitation of membrane-enriched fractions. Yeast tri-hybrid screen, co-immunoprecipitation from membrane-enriched fractions, SHP-1 activity assays Journal of immunology High 11160222
2001 Targeting activated SHP-1 to lipid rafts in T cells inhibits TCR-mediated signaling by causing rapid dephosphorylation of LAT (linker for activation of T cells), while leaving Lck kinase activity and TCR-ζ/ZAP-70 phosphorylation intact; endogenous SHP-1 is recruited to rafts and associates with LAT upon TCR engagement. Chimeric raft-targeting SHP-1 construct expressed in Jurkat cells, CD69 expression, signaling pathway analysis, co-immunoprecipitation of endogenous SHP-1 with LAT Immunity High 11420038
2002 Crystal structure of C-terminally truncated human SHP-1 at 2.8 Å resolution reveals an auto-inhibited conformation in which the N-SH2 domain blocks the catalytic domain active site, demonstrating that SHP-1 phosphatase activity is primarily regulated by intramolecular N-SH2 domain occlusion. X-ray crystallography The Journal of biological chemistry High 12482860
2002 Death receptors (TNF/NGF family) contain a conserved phosphotyrosine motif in their death domain that recruits SHP-1 (and SHP-2/SHIP) in a caspase-independent, cell-dependent manner; in neutrophils, SHP-1 recruited via this motif inactivates the anti-apoptotic kinase Lyn, preventing cytokine-induced survival signaling. Co-immunoprecipitation, phosphotyrosine motif mapping, Lyn kinase activity assay in neutrophils Nature medicine High 11786908
2002 SHP-1 associates with CBL in macrophages upon FcγR engagement; wild-type but not catalytically inactive SHP-1 overexpression dephosphorylates CBL, disrupts the CBL-CRKL interaction, suppresses RAC activation, and completely abrogates phagocytosis of IgG-sensitized targets. Heterologous expression of wild-type vs. catalytically inactive SHP-1, co-immunoprecipitation, RAC activation assay, phagocytosis assay Blood High 12176909
2003 SHP-1 forms complexes with TrkA at Y490 and dephosphorylates TrkA at Y674/675; SHP-1 expression in sympathetic neurons induces apoptosis and TrkA dephosphorylation, while dominant-inhibitory SHP-1 promotes NGF-independent survival; SHP-1-deficient mice have increased sympathetic neuron numbers during developmental cell death. Co-immunoprecipitation with phosphosite mapping, dominant-inhibitory SHP-1 expression, neuron survival assays, SHP-1-deficient motheaten mice The Journal of cell biology High 14662744
2003 SHP-1 transfection inhibits growth of lymphoma/leukemia and breast cancer cell lines, and SHP-1 down-regulates activated JAK kinase levels partly by accelerating TYK2 and JAK1 degradation via the proteasome-mediated pathway (blocked by MG132). SHP-1 transfection, cell growth assays, Western blot for JAK1/TYK2, proteasome inhibitor MG132 Journal of cellular biochemistry Medium 14624462
2004 SHP-1 dephosphorylates α-actinin in vitro and in vivo; it was purified from platelet lysates and identified by mass spectrometry as a 68 kDa phosphatase of α-actinin; co-transfection of SHP-1 with FAK and α-actinin abolishes α-actinin phosphorylation without substantially affecting FAK phosphorylation. Sequential chromatography purification, electrospray tandem mass spectrometry identification, in vitro dephosphorylation assay, co-transfection in COS-7 cells, catalytic mutant (C453S) The Journal of biological chemistry High 15070900
2006 SHP-1 deficiency (viable motheaten mice) results in markedly enhanced insulin receptor signaling via IRS-PI3K-Akt in liver and muscle; SHP-1 directly modulates hepatic insulin clearance by regulating CEACAM1 tyrosine phosphorylation. Adenoviral dominant-negative or shRNA-mediated SHP-1 silencing in liver recapitulates improved insulin sensitivity. Viable motheaten mice, adenoviral expression of catalytically inert SHP-1, shRNA knockdown, insulin signaling Western blots (IRS-PI3K-Akt), [125I]-insulin clearance assay, CEACAM1 phosphorylation in vitro Nature medicine High 16617349
2006 Leishmania donovani-activated SHP-1 inhibits IFN-γ-dependent nitric oxide production in macrophages by inactivating JAK2 and ERK1/2 and preventing nuclear translocation of NF-κB and AP-1; SHP-1-deficient macrophages fail to suppress nitric oxide in response to Leishmania. SHP-1-/- macrophage cell line (motheaten-derived), JAK2/ERK1/2 phosphorylation assay, nuclear translocation assays for NF-κB/AP-1, nitric oxide production assay Infection and immunity High 17057094
2007 FCRL5 inhibits BCR signaling by dual ITIM-dependent recruitment of SHP-1, which dephosphorylates the ITAM-based tyrosines in BCR Igα/Igβ heterodimers; ITIM tyrosine mutations abolish this effect. FCRL5-FcγRIIB chimeric construct expression in B cell line, ITIM mutational analysis, calcium mobilization assay, SHP-1 co-immunoprecipitation Proceedings of the National Academy of Sciences High 17522256
2007 PU.1, an Ets family transcription factor, directly binds the hematopoietic cell-specific P2 promoter of the SHP-1 gene and activates its transcription; siRNA-mediated depletion of PU.1 profoundly suppresses SHP-1 gene transcription. Luciferase reporter assays, EMSA (in vitro binding), ChIP (in vivo binding), PU.1 siRNA knockdown The Journal of biological chemistry High 17218319
2008 Leishmania activates SHP-1 to directly inactivate IRAK-1 kinase activity by binding via an evolutionarily conserved ITIM-like motif (KTIM) in the kinase domain of IRAK-1; SHP-1 also interacts with ERK1/2 and IKKα/β via similar KTIM motifs. Co-immunoprecipitation of SHP-1 with IRAK-1, IRAK-1 kinase activity assay, KTIM motif mutational analysis, Leishmania infection model PLoS neglected tropical diseases High 19104650
2010 SHP-1 phosphorylation at Tyr536 and Tyr564 by Lyn kinase is required for maximal SHP-1 phosphatase activity; Tyr564 phosphorylation by Lyn is indispensable for suppression of Stat5 activity and prevention of CMML-like myeloproliferative disease; Tyr536 is required for efficient SHP-1 interaction with Stat5. PLC-β3 acts upstream of this Lyn/SHP-1 regulatory axis. Lyn/PLC-β3 double-knockout mice, phosphorylation-defective SHP-1 mutants (Y536F, Y564F), SHP-1 activity assay, co-immunoprecipitation, Stat5 activity assay Blood High 20858858
2011 Combinatorial peptide library screening established that SHP-1 has narrow substrate specificity with strong preference for acidic and aromatic hydrophobic residues on both sides of pY, requiring acidic residues at pY-1 and pY+1 and no basic residues; this intrinsic specificity correlates well with known in vivo substrates. On-bead combinatorial peptide library screening, solution-phase kinetic analysis of individually synthesized phosphotyrosyl peptides Biochemistry High 21291263
2011 Crystal structure of full-length SHP-1 at 3.1 Å reveals an open conformation in which the N-SH2 domain is shifted away from the active site, exposing the catalytic pocket; the C-SH2 domain is twisted ~110° relative to the autoinhibited structure; new interdomain interactions stabilize the open conformation. X-ray crystallography of full-length SHP-1 Journal of cellular biochemistry High 21465528
2012 SHP-1 is recruited to phagosomes early after phagocytosis and remains present for up to 4 h; loss of SHP-1 impairs phagosome acidification and prevents processing of procathepsin D (51 kDa) to cathepsin D (46 kDa) and reduces LAMP-1 recruitment, demonstrating a role for SHP-1 in phagolysosome biogenesis. Confocal immunofluorescence microscopy, Western blot on purified phagosome extracts, LysoTracker pH indicator, SHP-1-deficient motheaten macrophages Journal of immunology High 22826316
2012 FcγRIII on neutrophils recruits SHP-1 upon IVIG engagement to mediate inhibition of neutrophil adhesion and activation; this inhibitory signaling is abrogated in SHP-1-mutant mice, demonstrating an unexpected inhibitory role for the classic activating receptor FcγRIII via SHP-1. Intravital microscopy, FcγRIII/FcγRIIB-deficient mice, SHP-1-mutant mice, co-immunoprecipitation Circulation research High 22415018
2013 SHP-1 decreases STAT3 phosphorylation in CD4+ T cells in response to IL-6 and IL-21; genetic deletion, transgenic dominant-negative, or pharmacologic inhibition of SHP-1 strongly promotes Th17 development, identifying SHP-1 as a negative regulator of STAT3-driven Th17 differentiation. T cell-specific SHP-1 knockout, inducible dominant-negative SHP-1 transgenic mice, pharmacologic SHP-1 inhibition, Th17 skewing assays, STAT3 phosphorylation assay Blood High 22438258
2014 Regorafenib activates SHP-1 by directly disrupting the autoinhibitory association between the N-SH2 and catalytic PTP domain of SHP-1; deletion of N-SH2 (dN1) or D61A point mutation blocks regorafenib-induced SHP-1 activation and STAT3(Tyr705) dephosphorylation. SHP-1 activity assay, N-SH2 deletion and D61A point mutation constructs, Western blot for p-STAT3, xenograft tumor model Oncotarget High 25071018
2015 SHP-1 is recruited to and dephosphorylates Cbl-b upon TCR stimulation; loss of SHP-1 in T cells leads to increased Cbl-b tyrosine phosphorylation, ubiquitination, and degradation. CD28 costimulation abrogates SHP-1/Cbl-b interaction, linking this mechanism to T cell activation control. Co-immunoprecipitation of SHP-1 with Cbl-b, phosphorylation and ubiquitination Western blots, T cell-specific Shp1-/- mice, Cbl-b overexpression rescue Journal of immunology High 26416283
2015 SHP-1 co-localizes with and binds to TRPV1 in DRG nociceptive neurons and dephosphorylates TRPV1, reducing channel activity; pharmacological inhibition of SHP-1 sensitizes TRPV1 and induces thermal hyperalgesia in vivo. Co-immunoprecipitation of SHP-1 with TRPV1, whole-cell patch clamp of DRG neurons, intrathecal SHP-1 inhibitor injection, SHP-1 overexpression in DRG neurons Pain High 25790452
2015 SHP-1 phosphatase activity (requiring N-SH2 domain and catalytic activity via D61A-constitutively-open mutant) directly dephosphorylates STAT3 at Tyr705 to suppress TGF-β1-induced epithelial-mesenchymal transition in hepatocellular carcinoma cells. SHP-1 overexpression/knockdown, constitutively open (D61A) and catalytic dead (C453S) SHP-1 mutants, TGF-β1 stimulation, p-STAT3 Western blot, migration/invasion assays Oncogene High 25619838
2016 Protein kinase D (PKD) phosphorylates SHP-1 directly; substitution of wild-type SHP-1 with phosphorylation-defective mutant SHP-1 S557A impairs CD4+ thymocyte generation, placing the PKD–SHP-1 axis as a positive regulator of TCR signaling during positive selection. PKD2/PKD3 double-deficient mice, phosphoproteomic substrate identification of SHP-1, SHP-1 S557A knock-in, T cell development analysis Nature communications High 27670070
2018 SHP-1 interacts with the ITIM on TGF-β receptor 1 and is required for TGF-β signaling activation in hematopoietic stem cells (HSCs); Shp-1 knockout HSCs fail to respond to TGF-β-enforced quiescence, demonstrating SHP-1 as a positive mediator of TGF-β–driven HSC quiescence. Shp-1 knockout mice, co-immunoprecipitation of SHP-1 with TGFβR1, in vitro and in vivo HSC quiescence/TGF-β response assays The Journal of experimental medicine High 29669741
2018 SHP-1 inhibits JAK/STAT, NF-κB, and AKT (but not MAPK) signaling in hepatocytes and HCC cells; hepatocyte-specific Ptpn6 knockout enhances DEN-induced hepatocarcinogenesis and liver cancer metastasis in mice. Conditional Ptpn6 knockout in hepatocytes, adenoviral SHP-1 delivery, signaling pathway Western blots, DEN-induced tumor model, orthotopic HCC model Cancer research High 29776962
2019 Ptpn6 in neutrophils negatively regulates p38 MAPK-dependent production of TNF and IL-1α/β, and maintains Ripk1 function to prevent caspase-8- and Ripk3/Mlkl-dependent cell death and IL-1α/β release; combined deletion of caspase-8 and Ripk3 or Mlkl strongly protects Ptpn6-deficient neutrophils from inflammatory disease. Conditional Ptpn6 deletion in neutrophils, genetic deletion of Ripk1, Ripk3, Mlkl, caspase-8 in Ptpn6ΔPMN background, p38 MAPK activity assay, IL-1 and TNF measurement Nature immunology High 31819256
2020 PD-L1 activates SHP-1 in DRG TRPV1+ nociceptive neurons; SHP-1 inhibits TRPV1 currents and bone cancer pain. Conditional deletion of SHP-1 in NaV1.8+ neurons aggravates bone cancer pain and abolishes PD-L1-mediated inhibition of TRPV1 currents. Conditional SHP-1 deletion in NaV1.8+ neurons, patch-clamp recording of TRPV1 currents, PD-L1 injection, bone cancer pain behavioral assay, PD-1/TRPV1/SHP-1 co-localization JCI insight High 32960817
2020 DJ-1 facilitates the interaction between SHP-1 and TRAF6 in astrocytes during cerebral ischemia/reperfusion; SHP-1/TRAF6 interaction promotes dissociation of NLRX1 from TRAF6 and reduces inflammatory cytokine production; a SHP-1 inhibitor blocks this DJ-1-dependent anti-inflammatory effect. Co-immunoprecipitation of SHP-1 with TRAF6 and NLRX1, DJ-1 knockdown/overexpression, SHP-1 inhibitor, OGD/R and MCAO/R models Journal of neuroinflammation Medium 32151250
2022 SKAP2 forms a complex with Sirpα and SHP-1 and recruits the Sirpα/SHP-1 complex to TLR4 to attenuate NF-κB inflammatory signaling; SKAP2 also directly associates with MyD88/TIRAP/TRAM adaptors of TLR4. Co-immunoprecipitation of SKAP2-Sirpα-SHP-1 complex, SKAP2 knockout mice, NF-κB activity assays, LPS stimulation model Oncogene Medium 35034964
2022 SHP-1 interacts with ER-resident STING and suppresses K63-linked ubiquitination and activation of STING; SHP-1 knockdown leads to STING overactivation, which inhibits AMPK and represses mitochondrial biogenesis in RPE cells. Immunoprecipitation to detect SHP-1-STING interaction and STING ubiquitination, STING-specific antagonist H151, SHP-1 lentiviral knockdown, AMPK/mitochondrial biogenesis assays Molecular medicine Medium 36273174
2023 SHP-1 reduces SUMO2 post-translational modification of podocin; podocyte-specific SHP-1 deletion preserves slit diaphragm protein complexes and prevents diabetes-induced podocyte loss and diabetic kidney disease progression, revealing a role for SHP-1 in regulating cytoskeleton dynamics and slit diaphragm stability. Conditional podocyte-specific Ptpn6 knockout mice, mass spectrometry SUMOylation analysis, albumin/creatinine ratio, glomerular morphology, Western blots for slit diaphragm proteins Kidney international High 37507049
2024 SHP-1 inhibition in leukemia stem cells upregulates PFKP via the AKT–β-catenin pathway, increasing glycolysis and oxidative phosphorylation; elevated PFKP also promotes MYC degradation, reducing immune evasion. This dual mechanism enhances chemosensitivity and immunosurveillance of LSCs. SHP-1 inhibition in LSCs, AKT-β-catenin pathway analysis, PFKP expression assays, MYC degradation assay, metabolic activity assays, in vivo AML models Nature cell biology High 38321204

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell 656 8324828
1997 Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling. Cell 380 9244303
1996 Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling. Science (New York, N.Y.) 348 8638162
2009 SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunological reviews 304 19290938
2000 Roles of the SHP-1 tyrosine phosphatase in the negative regulation of cell signalling. Seminars in immunology 263 10995583
2003 The function of the protein tyrosine phosphatase SHP-1 in cancer. Gene 237 12657462
2002 Death receptors bind SHP-1 and block cytokine-induced anti-apoptotic signaling in neutrophils. Nature medicine 151 11786908
2002 Crystal structure of human protein-tyrosine phosphatase SHP-1. The Journal of biological chemistry 145 12482860
2005 A SHPing tale: perspectives on the regulation of SHP-1 and SHP-2 tyrosine phosphatases by the C-terminal tail. Cellular signalling 144 16084691
1997 Src kinase activity is regulated by the SHP-1 protein-tyrosine phosphatase. The Journal of biological chemistry 141 9261115
2000 RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia. Human molecular genetics 133 11001933
1997 Severe defects in immunity and hematopoiesis caused by SHP-1 protein-tyrosine-phosphatase deficiency. Trends in biotechnology 133 9263478
1999 SHP-1 regulates Lck-induced phosphatidylinositol 3-kinase phosphorylation and activity. The Journal of biological chemistry 122 10488096
2006 The SHP-1 protein tyrosine phosphatase negatively modulates glucose homeostasis. Nature medicine 112 16617349
2013 SHP-1 phosphatase activity counteracts increased T cell receptor affinity. The Journal of clinical investigation 104 23391724
2000 Cytoplasmic protein tyrosine phosphatases SHP-1 and SHP-2: regulators of B cell signal transduction. Current opinion in immunology 103 10781410
1995 Human protein tyrosine phosphatase 1C (PTPN6) gene structure: alternate promoter usage and exon skipping generate multiple transcripts. Genomics 98 7665165
1999 Regulation of acidification and apoptosis by SHP-1 and Bcl-2. The Journal of biological chemistry 95 10506221
1998 Regulation of angiotensin II-induced JAK2 tyrosine phosphorylation: roles of SHP-1 and SHP-2. The American journal of physiology 93 9814969
2006 Role of host protein tyrosine phosphatase SHP-1 in Leishmania donovani-induced inhibition of nitric oxide production. Infection and immunity 92 17057094
2007 Fc receptor-like 5 inhibits B cell activation via SHP-1 tyrosine phosphatase recruitment. Proceedings of the National Academy of Sciences of the United States of America 90 17522256
2011 Substrate specificity of protein tyrosine phosphatases 1B, RPTPα, SHP-1, and SHP-2. Biochemistry 87 21291263
2011 Crystal structure of human protein tyrosine phosphatase SHP-1 in the open conformation. Journal of cellular biochemistry 86 21465528
1999 Inhibitory roles for SHP-1 and SOCS-3 following pituitary proopiomelanocortin induction by leukemia inhibitory factor. The Journal of clinical investigation 81 10545526
2003 SHP-1 negatively regulates neuronal survival by functioning as a TrkA phosphatase. The Journal of cell biology 80 14662744
2001 Involvement of SHP-1 tyrosine phosphatase in TCR-mediated signaling pathways in lipid rafts. Immunity 80 11420038
2008 Leishmania-induced IRAK-1 inactivation is mediated by SHP-1 interacting with an evolutionarily conserved KTIM motif. PLoS neglected tropical diseases 77 19104650
2003 SHP-1 suppresses cancer cell growth by promoting degradation of JAK kinases. Journal of cellular biochemistry 75 14624462
2018 SHP-1 Acts as a Tumor Suppressor in Hepatocarcinogenesis and HCC Progression. Cancer research 73 29776962
2005 SHP-1 promoter 2 methylation in normal epithelial tissues and demethylation in psoriasis. Journal of molecular medicine (Berlin, Germany) 73 16389548
2011 Alteration in the gene encoding protein tyrosine phosphatase nonreceptor type 6 (PTPN6/SHP1) may contribute to neutrophilic dermatoses. The American journal of pathology 69 21406173
2000 Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1. The Journal of biological chemistry 68 10660565
1998 The protein tyrosine phosphatase SHP-1 regulates integrin-mediated adhesion of macrophages. Current biology : CB 67 9740804
2006 Investigations into the regulation and function of the SH2 domain-containing protein-tyrosine phosphatase, SHP-1. Immunologic research 63 17003515
2005 Leishmania donovani engages in regulatory interference by targeting macrophage protein tyrosine phosphatase SHP-1. Clinical immunology (Orlando, Fla.) 62 15721837
1997 Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes. The Journal of experimental medicine 62 9348315
2011 SHP-1 in cell-cycle regulation. Anti-cancer agents in medicinal chemistry 61 21291405
2010 Novel SHP-1 inhibitors tyrosine phosphatase inhibitor-1 and analogs with preclinical anti-tumor activities as tolerated oral agents. Journal of immunology (Baltimore, Md. : 1950) 61 20421638
1999 Deficiency of SHP-1 protein-tyrosine phosphatase activity results in heightened osteoclast function and decreased bone density. The American journal of pathology 60 10393854
2002 SHP-1 regulates Fcgamma receptor-mediated phagocytosis and the activation of RAC. Blood 59 12176909
2001 Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells. Journal of immunology (Baltimore, Md. : 1950) 58 11160222
2000 The protein-tyrosine phosphatase SHP-1 binds to and dephosphorylates p120 catenin. The Journal of biological chemistry 58 10835420
2018 Targeting SHP-1, 2 and SHIP Pathways: A Novel Strategy for Cancer Treatment? Oncology 56 29925063
2010 Lyn- and PLC-beta3-dependent regulation of SHP-1 phosphorylation controls Stat5 activity and myelomonocytic leukemia-like disease. Blood 55 20858858
2015 SHP-1 is a negative regulator of epithelial-mesenchymal transition in hepatocellular carcinoma. Oncogene 53 25619838
2019 Ptpn6 inhibits caspase-8- and Ripk3/Mlkl-dependent inflammation. Nature immunology 52 31819256
1997 Protein-tyrosine phosphatase SHP-1 is dispensable for FcgammaRIIB-mediated inhibition of B cell antigen receptor activation. The Journal of biological chemistry 52 9242674
2018 SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-β signaling. The Journal of experimental medicine 51 29669741
2014 SHP-1 plays a crucial role in CD40 signaling reciprocity. Journal of immunology (Baltimore, Md. : 1950) 51 25187664
2000 Evidence of a role for SHP-1 in platelet activation by the collagen receptor glycoprotein VI. The Journal of biological chemistry 51 10871605
2021 Fangchinoline diminishes STAT3 activation by stimulating oxidative stress and targeting SHP-1 protein in multiple myeloma model. Journal of advanced research 50 35024200
2000 Expression and function of the protein tyrosine phosphatase SHP-1 in oligodendrocytes. Glia 50 10652447
1998 Reversible regulation of SHP-1 tyrosine phosphatase activity by oxidation. Biochemistry and molecular biology international 49 9739453
2020 Inhibition of TRPV1 by SHP-1 in nociceptive primary sensory neurons is critical in PD-L1 analgesia. JCI insight 48 32960817
2014 Hyperinsulinemia induces insulin resistance and immune suppression via Ptpn6/Shp1 in zebrafish. The Journal of endocrinology 46 24904114
2014 SHP-1 is a target of regorafenib in colorectal cancer. Oncotarget 46 25071018
2015 Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats. Pain 45 25790452
2013 Deficiency in hematopoietic phosphatase ptpn6/Shp1 hyperactivates the innate immune system and impairs control of bacterial infections in zebrafish embryos. Journal of immunology (Baltimore, Md. : 1950) 45 23335748
2020 DJ-1 exerts anti-inflammatory effects and regulates NLRX1-TRAF6 via SHP-1 in stroke. Journal of neuroinflammation 44 32151250
2011 SHP-1 expression accounts for resistance to imatinib treatment in Philadelphia chromosome-positive cells derived from patients with chronic myeloid leukemia. Blood 44 21821701
2016 SHP-1: the next checkpoint target for cancer immunotherapy? Biochemical Society transactions 43 27068940
1999 SHP-1 regulation of p62(DOK) tyrosine phosphorylation in macrophages. The Journal of biological chemistry 40 10585470
2012 Intravenous immunoglobulins modulate neutrophil activation and vascular injury through FcγRIII and SHP-1. Circulation research 39 22415018
2023 Targeting pathogenic macrophages by the application of SHP-1 agonists reduces inflammation and alleviates pulmonary fibrosis. Cell death & disease 38 37291088
2015 Protein Tyrosine Phosphatase SHP-1 Modulates T Cell Responses by Controlling Cbl-b Degradation. Journal of immunology (Baltimore, Md. : 1950) 38 26416283
1999 Defective expression of the SHP-1 phosphatase in polycythemia vera. Experimental hematology 38 10390187
2017 The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells. Experimental & molecular medicine 37 28798401
2010 Deficient SOCS3 and SHP-1 expression in psoriatic T cells. The Journal of investigative dermatology 37 20130595
2004 FLT3/ITD mutation signaling includes suppression of SHP-1. The Journal of biological chemistry 37 15574429
2014 Methylation and decreased expression of SHP-1 are related to disease progression in chronic myelogenous leukemia. Oncology reports 35 24647617
2009 SHP-1 deficient mast cells are hyperresponsive to stimulation and critical in initiating allergic inflammation in the lung. Journal of immunology (Baltimore, Md. : 1950) 35 20042576
2006 SHP-1 inhibits LPS-mediated TNF and iNOS production in murine macrophages. Biochemical and biophysical research communications 35 16487932
2006 Age-related impairment of GM-CSF-induced signalling in neutrophils: role of SHP-1 and SOCS proteins. Ageing research reviews 35 17142110
2013 Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes. American journal of physiology. Endocrinology and metabolism 33 23531619
2024 SHP-1 inhibition targets leukaemia stem cells to restore immunosurveillance and enhance chemosensitivity by metabolic reprogramming. Nature cell biology 32 38321204
2010 The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells. Journal of immunology (Baltimore, Md. : 1950) 32 20952680
2005 RNA interference targeting SHP-1 attenuates myocardial infarction in rats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 16223786
2016 Protein tyrosine phosphatase SHP-1: resurgence as new drug target for human autoimmune disorders. Immunologic research 31 27216862
2010 Elevated expression of the tyrosine phosphatase SHP-1 defines a subset of high-grade breast tumors. Oncology 31 20090381
2003 SHP-1: a regulator of neutrophil apoptosis. Seminars in immunology 30 14563118
2021 Dynamic variability in SHP-1 abundance determines natural killer cell responsiveness. Science signaling 29 34752140
2016 Protein kinase D regulates positive selection of CD4+ thymocytes through phosphorylation of SHP-1. Nature communications 29 27670070
2011 The SHP-1 protein tyrosine phosphatase negatively modulates Akt signaling in the ghrelin/GHSR1a system. Molecular biology of the cell 29 21900501
2022 SHP-1 knockdown suppresses mitochondrial biogenesis and aggravates mitochondria-dependent apoptosis induced by all trans retinal through the STING/AMPK pathways. Molecular medicine (Cambridge, Mass.) 28 36273174
2014 The SHP-1 expression is associated with cytokines and psychopathological status in unmedicated first episode schizophrenia patients. Brain, behavior, and immunity 28 24793756
2004 The protein-tyrosine phosphatase SHP-1 regulates the phosphorylation of alpha-actinin. The Journal of biological chemistry 28 15070900
2012 The tyrosine phosphatase SHP-1 dampens murine Th17 development. Blood 27 22438258
2008 A critical role of SHP-1 in regulation of type 2 inflammation in the lung. American journal of respiratory cell and molecular biology 27 18952567
2007 PU.1 activates transcription of SHP-1 gene in hematopoietic cells. The Journal of biological chemistry 27 17218319
2023 Deletion of protein tyrosine phosphatase SHP-1 restores SUMOylation of podocin and reverses the progression of diabetic kidney disease. Kidney international 26 37507049
2022 SKAP2 suppresses inflammation-mediated tumorigenesis by regulating SHP-1 and SHP-2. Oncogene 26 35034964
2008 SHP-1 inhibition by 4-hydroxynonenal activates Jun N-terminal kinase and glutamate cysteine ligase. American journal of respiratory cell and molecular biology 26 18276794
1998 SHP-1 phosphatase C-terminus interacts with novel substrates p32/p30 during erythropoietin and interleukin-3 mitogenic responses. Blood 26 9573011
1992 Assignment of a novel protein tyrosine phosphatase gene (Hcph) to mouse chromosome 6. Genomics 26 1427910
1997 Regulation of cell signaling by the protein tyrosine phosphatases, CD45 and SHP-1. Immunologic research 25 9048211
2017 Crocin Suppresses Constitutively Active STAT3 Through Induction of Protein Tyrosine Phosphatase SHP-1. Journal of cellular biochemistry 23 28295507
2016 Akt and SHP-1 are DC-intrinsic checkpoints for tumor immunity. JCI insight 23 27812544
2001 Mutation of the hematopoietic cell phosphatase (Hcph) gene is associated with resistance to gamma-irradiation-induced apoptosis in Src homology protein tyrosine phosphatase (SHP)-1-deficient "motheaten" mutant mice. Journal of immunology (Baltimore, Md. : 1950) 23 11145649
2022 Ethyl Gallate Dual-Targeting PTPN6 and PPARγ Shows Anti-Diabetic and Anti-Obese Effects. International journal of molecular sciences 22 35563411
2012 The protein tyrosine phosphatase SHP-1 regulates phagolysosome biogenesis. Journal of immunology (Baltimore, Md. : 1950) 22 22826316

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