Affinage

INPP5D

Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 · UniProt Q92835

Length
1189 aa
Mass
133.3 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

INPP5D/SHIP1 is a hematopoietic-enriched inositol 5-phosphatase that hydrolyzes PtdIns(3,4,5)P3 to PtdIns(3,4)P2 at the plasma membrane and on phagosomal membranes, thereby serving as a master negative regulator of PI3K/Akt signaling downstream of diverse immune receptors including BCR/FcγRIIB, FcεRI, TREM2/DAP12, GPVI, integrins, TLRs, and TIGIT (PMID:9586640, PMID:9852043, PMID:20484116, PMID:23154388). SHIP1 is recruited to receptors via its SH2 domain binding to phosphorylated ITIMs and ITAMs, is activated by Lyn-mediated tyrosine phosphorylation and PKA-dependent Ser440 phosphorylation, and requires both its catalytic domain and C-terminal proline-rich region for full enzymatic function; its C-terminus also mediates autoinhibitory intramolecular interactions that regulate SH2-domain accessibility (PMID:11016922, PMID:12882960, PMID:20810657, PMID:11222379, PMID:22182704). By controlling local PIP3 pools, SHIP1 governs Btk and Tec membrane localization, Ca²⁺ mobilization, neutrophil polarity and chemotaxis, phagosome maturation and NADPH oxidase activation, NLRP3 inflammasome suppression, NK cell cytotoxicity, endotoxin tolerance, and cell cycle progression through Akt-dependent cyclin D/p27 regulation (PMID:9820480, PMID:17173042, PMID:18490750, PMID:38016942, PMID:15604218, PMID:15308103, PMID:17142780). SHIP1 functions as a tumor suppressor in B cells—cooperating with PTEN to prevent lymphomagenesis—and its reduced expression or activity in microglia enhances amyloid-β phagocytosis and inflammasome activation, linking INPP5D to Alzheimer's disease pathology (PMID:20956547, PMID:37061460, PMID:38016942).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1997 High

    Establishing that SHIP1 is an enzymatically active inositol 5-phosphatase that reduces PIP3 levels in vivo and that its catalytic activity is required to inhibit PI3K-dependent signaling resolved the question of whether SHIP1 functions as a lipid phosphatase rather than merely an adaptor protein.

    Evidence Injection of wild-type vs. catalytically inactive SHIP cRNA into Xenopus oocytes with GVBD, MAPK, and lipid measurements

    PMID:9111325

    Open questions at the time
    • Structural basis of catalytic specificity not determined
    • In vivo relevance in mammalian hematopoietic cells not yet shown
  2. 1997 High

    Demonstrating that SHIP1 mediates FcγRIIB inhibitory signaling in B cells—distinct from SHP-1-mediated KIR signaling—established SHIP1 as the phosphatase specifically recruited by the FcγRIIB ITIM to modulate BCR co-inhibition.

    Evidence Genetic deletion of SHIP or SHP-1 in B cell lines with inhibitory signaling and apoptosis readouts

    PMID:9244303

    Open questions at the time
    • Mechanism of SHIP1 recruitment to FcγRIIB ITIM not yet mapped at the residue level
  3. 1998 High

    Showing that SHIP1 controls Btk membrane association and Akt activation by depleting PIP3 downstream of BCR/FcγRIIB defined the core mechanistic axis: SHIP1 → PIP3 depletion → loss of PH-domain-dependent effector membrane recruitment → signal termination.

    Evidence SHIP-deficient DT40 B cells with membrane-anchored Btk rescue, PIP3 quantification, Ca²⁺ flux, and Akt kinase assays

    PMID:9586640 PMID:9820480 PMID:9852043

    Open questions at the time
    • Whether PI(3,4)P2 generated by SHIP1 has independent signaling roles was unclear
    • Contribution of SHIP1 vs. SHIP2 not delineated
  4. 2000 High

    Residue-level mapping of ITIM determinants (Y+2 leucine for SHIP binding vs. Y−2 isoleucine for SHP binding) and identification of SH2-dependent recruitment to EPO-R and a DOK1/CRKL signaling complex defined how SHIP1 is recruited to multiple receptor systems and participates in multiprotein signaling complexes.

    Evidence ITIM residue substitution mutagenesis; EPO-R deletion/tyrosine mutants with co-IP; GST pulldown and migration assays in BCR/ABL-transformed cells

    PMID:10660611 PMID:11016922 PMID:11031258

    Open questions at the time
    • Crystal structure of SH2/ITIM interaction not available
    • Relative contribution of DOK1/CRKL complex to SHIP1 function in vivo unknown
  5. 2001 High

    Reconstitution experiments with domain mutants in SHIP−/− mast cells revealed that the C-terminal proline-rich region is essential for PIP3 hydrolysis and degranulation inhibition, even though the catalytic domain is intact, indicating the C-terminus is required for full enzymatic activity in cells.

    Evidence Retroviral transduction of wild-type, phosphatase-dead, C-terminal truncation, and NPXY mutant SHIP constructs into SHIP−/− BMMCs with PIP3, Ca²⁺, and degranulation readouts

    PMID:11222379

    Open questions at the time
    • Whether C-terminus acts through allosteric activation, membrane targeting, or protein–protein interactions not resolved
  6. 2003 High

    Identification of Lyn as a direct binding partner and activating kinase for SHIP1 via SH2-domain interaction, and discovery of a somatic V684E mutation reducing catalytic activity in leukemia, established the Lyn→SHIP1 activation axis and SHIP1's role as a tumor suppressor.

    Evidence GST-SH2 pulldowns, co-IP in macrophages, SHIP1−/− and Lyn−/− mice for Akt readouts; in vitro phosphatase assay with V684E mutant and proliferation assays in K562 cells

    PMID:12529653 PMID:12882960

    Open questions at the time
    • Frequency of SHIP1 mutations across leukemia subtypes not established
    • Whether other Src kinases can substitute for Lyn in different cell types unclear
  7. 2004 High

    Multiple studies using SHIP1−/− and Lyn−/− cells across mast cells, platelets, and NK cells established that Lyn-dependent SHIP1 activation is a general negative regulatory module controlling PIP3/Ca²⁺ in FcεRI signaling, integrin outside-in signaling, and IFN-γ production, while LPS tolerance was shown to require SHIP1 upregulation by autocrine TGFβ.

    Evidence SHIP1−/− and Lyn−/− BMMCs, platelets, NK cells; PIP3 and Ca²⁺ measurements; IFN-γ assays with catalytic-dead mutant; LPS tolerance in SHIP−/− macrophages with TGFβ neutralization

    PMID:15166241 PMID:15210764 PMID:15308103 PMID:15492005 PMID:15604218

    Open questions at the time
    • Endotoxin tolerance mechanism beyond SHIP1 upregulation (e.g., chromatin remodeling) not addressed
    • Whether SHIP1-Tec interaction is relevant in primary cells not confirmed
  8. 2006 High

    Live PIP3 biosensor imaging in SHIP1−/− neutrophils demonstrated that SHIP1 restricts PIP3 to the leading edge to establish cell polarity during chemotaxis—a function not shared by PTEN—resolving the question of which phosphatase controls spatial PIP3 distribution in neutrophils.

    Evidence SHIP1−/− mice crossed with AktPH-GFP transgenic biosensor mice; time-lapse chemotaxis imaging

    PMID:17173042

    Open questions at the time
    • Whether SHIP1 and PTEN have cooperative roles in other migratory cell types not tested
  9. 2007 High

    Live imaging of YFP-SHIP1 at forming phagosomes showed SHIP1 is recruited early and dissociates before PI3K, establishing temporal control of PIP3 on phagosomes; separately, identification of allosteric small-molecule SHIP1 agonists protective in endotoxemia and anaphylaxis demonstrated druggability.

    Evidence Live-cell imaging of YFP-SHIP1 and PI3K-CFP chimeras during phagocytosis; in vitro enzyme assays with allosteric activators; in vivo mouse models

    PMID:17442886 PMID:17502453

    Open questions at the time
    • Identity of the allosteric activation domain not structurally defined
    • SHIP1 agonist selectivity over SHIP2 not fully characterized
  10. 2008 High

    Demonstration that SHIP1-generated PI(3,4)P2 on phagosomes activates NADPH oxidase for the early oxidative burst, and that SHIP1 loss disrupts Rab5a/PI(3)P dynamics, established that SHIP1's product PI(3,4)P2 has positive signaling functions beyond simply depleting PIP3.

    Evidence SHIP1−/− macrophages with phagosomal phospholipid quantification, ROS imaging, and phagosome maturation markers

    PMID:18490750

    Open questions at the time
    • Direct PI(3,4)P2 effectors on the phagosome not identified
    • Whether PI(3,4)P2 signaling differs between phagosomes and plasma membrane not resolved
  11. 2009 High

    Identification of miR-155 as a direct repressor of SHIP1 mRNA driving DLBCL proliferation, and of a Lyn/PKC-δ/SHIP1 signaling complex specific to GPVI in platelets, expanded SHIP1 regulation to post-transcriptional control and receptor-specific signaling complexes.

    Evidence miR-155 target validation in DLBCL with anti-TNFα rescue and xenograft models; co-IP from Lyn−/− and PKC-δ−/− platelets with SHIP1 phosphorylation and dense granule secretion assays

    PMID:19587372 PMID:19890474

    Open questions at the time
    • Whether miR-155/SHIP1 axis is relevant beyond DLBCL not established
    • Other miRNAs targeting SHIP1 not surveyed
  12. 2010 High

    Multiple 2010 studies established that SHIP1 cooperates with PTEN as a tumor suppressor in B cells (double KO causes spontaneous lymphoma), is activated by PKA at Ser440, inhibits TREM2/DAP12 signaling via SH2-dependent DAP12 binding, and suppresses AML progenitor proliferation in a catalytic-activity-dependent manner.

    Evidence B-cell-specific PTEN/SHIP conditional double-KO mice; mass spectrometry identification of Ser440 with S440A mutagenesis in DT40 cells; SHIP1 SH2-domain mutants and knockdown in TREM2/DAP12 reconstitution; lentiviral WT/D672A SHIP1 in AML CD34+ cells

    PMID:19148132 PMID:20484116 PMID:20810657 PMID:20956547

    Open questions at the time
    • Structural basis for PKA-mediated allosteric activation not resolved
    • Whether SHIP1 loss alone is sufficient for lymphomagenesis without PTEN loss unknown
  13. 2011 Medium

    FRET-based studies revealed that the SHIP1 C-terminus engages in intramolecular interaction with the SH2 domain, creating an autoinhibited conformation that limits ITAM binding, providing a structural explanation for why the C-terminus is required for regulated enzymatic function.

    Evidence FRET in S2 cells; phospho-ITAM peptide pulldowns comparing full-length vs. isolated SH2 domain; membrane translocation assays

    PMID:22182704

    Open questions at the time
    • No high-resolution structural data for autoinhibited SHIP1
    • Physiological signals that relieve autoinhibition not identified
  14. 2012 High

    SHIP1 was placed in the TIGIT inhibitory pathway (recruited via Grb2 to phospho-Y225) to terminate PI3K/MAPK signaling in NK cells, and in a CD2AP/SHIP1 complex that inhibits Cbl E3 ligase activity in pDCs, expanding SHIP1's non-catalytic scaffolding roles.

    Evidence TIGIT Y225 mutants, Grb2/SHIP1 co-IP, SHIP1 siRNA in NK cytotoxicity assays; CD2AP/SHIP1 co-IP/MS with Cbl ubiquitin ligase assays in pDCs

    PMID:22706086 PMID:23154388

    Open questions at the time
    • Whether SHIP1 catalytic activity is required for TIGIT-mediated inhibition not tested
    • CD2AP/SHIP1 interaction not validated in other immune cell types
  15. 2014 Medium

    Cell-type-specific conditional knockouts revealed that SHIP1 in mesenchymal stem cells (not osteoclasts) drives the osteoporotic phenotype of SHIP1-null mice by limiting PI3K/Akt/β-catenin/Id2, and that SHIP1 associates with Fas to suppress Caspase-8-mediated T cell death, broadening SHIP1 biology beyond hematopoietic signaling.

    Evidence MSC-specific vs. myeloid-specific SHIP1 conditional KO mice with bone densitometry and pathway analysis; Fas co-IP and Caspase-8 inhibitor rescue in CD4Cre SHIP1 conditional KO mice

    PMID:24781051 PMID:24857423

    Open questions at the time
    • Mechanism by which SHIP1 interacts with Fas not defined
    • Whether SHIP1 catalytic activity is required for Fas-associated function not tested
  16. 2022 High

    Studies in Alzheimer's disease models demonstrated that SHIP1 haploinsufficiency or microglial-specific deletion enhances microglial phagocytosis and amyloid-β clearance, preserves cognition, and protects against plaque-induced neuronal dystrophy, establishing microglial SHIP1 as a negative regulator of protective microglial responses in AD.

    Evidence 5xFAD Inpp5d haploinsufficient mice and 5xFAD Inpp5dfl/fl Cx3cr1Ert2Cre conditional microglial KO with behavioral testing, plaque quantification, phagocytosis assays, and spatial transcriptomics

    PMID:36524682 PMID:37061460

    Open questions at the time
    • Whether SHIP1 reduction is beneficial long-term or has adverse immune consequences not established
    • Downstream effectors of enhanced microglial phagocytosis upon SHIP1 loss not identified
  17. 2023 High

    INPP5D/SHIP1 loss in human iPSC-derived microglia was shown to activate the NLRP3 inflammasome (Caspase-1, IL-1β, IL-18 secretion) and disrupt autophagy, with confirmation in human AD brain tissue, linking SHIP1 to inflammasome regulation in neurodegeneration.

    Evidence INPP5D disruption and pharmacological inhibition in iPSC-derived microglia; unbiased RNA/protein profiling; CASP1/IL-1β/IL-18 assays; human AD brain tissue analysis

    PMID:38016942

    Open questions at the time
    • Whether inflammasome activation is PIP3-dependent or involves a distinct SHIP1 mechanism not resolved
    • Relationship between enhanced phagocytosis and inflammasome activation upon SHIP1 loss not clarified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of full-length SHIP1 in autoinhibited and active conformations, the identity of direct PI(3,4)P2 effectors mediating SHIP1's product-dependent signaling, whether SHIP1 catalytic activity versus scaffolding functions are separable in vivo across cell types, and whether therapeutic SHIP1 modulation in microglia can be achieved without compromising peripheral immune homeostasis.
  • No full-length SHIP1 crystal or cryo-EM structure available
  • PI(3,4)P2-specific effectors downstream of SHIP1 not identified
  • Long-term consequences of microglial SHIP1 inhibition on peripheral immunity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 8 GO:0008289 lipid binding 5 GO:0098772 molecular function regulator activity 5
Localization
GO:0005886 plasma membrane 5 GO:0031410 cytoplasmic vesicle 2 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 5 R-HSA-109582 Hemostasis 2 R-HSA-5357801 Programmed Cell Death 2
Partners
BTKCD2APCRKLDOK1GRB2LYNPRKCDPSTPIP2
Complex memberships
CD2AP/SHIP1/CblDOK1/SHIP1/CRKL/PI3KLyn/SHIP1/PKC-δ (GPVI signaling complex)

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 SHIP (INPP5D) mediates FcγRIIB inhibitory signaling in B cells, distinct from SHP-1-mediated KIR inhibitory signaling; SHIP recruitment by FcγRIIB attenuates a proapoptotic signal initiated by FcγRIIB co-ligation to BCR, while SHP-1 blocks apoptosis via a separate pathway. Genetic deletion of SHIP or SHP-1 in B cell lines followed by functional inhibitory signaling assays and apoptosis measurements Cell High 9244303
1997 SHIP/SIP enzymatic activity (inositol 5-phosphatase) is required to inhibit PI3K-dependent signaling in vivo; catalytically inactive SHIP cannot block insulin- or PI3K-induced germinal vesicle breakdown or MAPK phosphorylation in Xenopus oocytes, and SHIP specifically reduces PtdIns(3,4,5)P3 levels generated in response to insulin. Injection of wild-type vs. catalytically inactive SHIP cRNA into Xenopus oocytes; GVBD and MAPK assays; lipid phosphoinositide measurements Molecular and cellular biology High 9111325
1998 SHIP reduces PIP3 levels upon FcγRIIB co-ligation with BCR, thereby regulating membrane association of Btk through PH domain–phosphoinositol lipid interactions; loss of SHIP increases Btk membrane association and hyperresponsive BCR signaling, while membrane-tethered Btk bypasses SHIP-mediated inhibition. Genetic deletion of SHIP in DT40 B cells; expression of membrane-anchored Btk chimera; PIP3 measurement; calcium flux assays Immunity High 9586640
1998 SHIP inhibits Akt/PKB activation downstream of BCR signaling by depleting PIP3; SHIP-deficient B cells show sustained Akt activity after FcγRIIB co-cross-linking, and PIP3 (not PI(3,4)P2) is the predominant in vivo activator of Akt. FcγRIIB ITIM mutants and SHIP-deficient B cells; Akt kinase activity assays; phosphatidylinositol 3-kinase-dependent signaling measurements The Journal of biological chemistry High 9852043
1998 SHIP-deficient DT40 B cells display enhanced and sustained Ca2+ mobilization (long-lasting Ca2+ oscillations) in response to BCR ligation, while ERK activation is unaffected, demonstrating SHIP modulates Ca2+ signaling specifically. SHIP knockout DT40 B cells; single-cell Ca2+ imaging; ERK activation assays Journal of immunology High 9820480
2000 SHIP1 and SHIP2 are recruited to FcγRIIB via ITIM binding determined by the Y+2 leucine residue in the FcγRIIB ITIM (distinct from the Y-2 isoleucine that determines SHP-1/SHP-2 binding), defining separate SHIP- and SHP-binding sites on ITIMs. Loss-of-function and gain-of-function ITIM residue substitutions between FcγRIIB and KIR ITIMs; in vivo recruitment assays The Journal of biological chemistry High 11016922
2000 SHIP1 forms a novel signaling complex with DOK1, PI3K, and CRKL in BCR/ABL-transformed cells; DOK1 binds directly through its PTB domain to SHIP1, and CRKL binds via its SH2 domain; Tyr917 and Tyr1020 in SHIP1 mediate interactions with DOK1 and regulate cell migration. Co-immunoprecipitation; GST pulldown; SHIP1 tyrosine mutants; migration assays in Ba/F3 cells The Journal of biological chemistry Medium 11031258
2000 Ship1 is recruited to the erythropoietin receptor (EPO-R) in an SH2-dependent manner at Tyr401 (with redundancy at Tyr429/Tyr431); EPO activates tyrosine phosphorylation of Ship1, leading to formation of a ternary Ship1/Shc/Grb2 complex. EPO-R deletion and tyrosine mutants; co-immunoprecipitation; kinase assays The Journal of biological chemistry Medium 10660611
2001 The C-terminus of SHIP (proline-rich region) is essential for its ability to hydrolyze PIP3 and inhibit mast cell degranulation; C-terminally truncated SHIP cannot revert SHIP-deficient BMMC responses even though the catalytic domain is intact. The catalytic phosphatase activity is required for inhibition; the NPXY motifs that bind Shc are dispensable. Retroviral infection of SHIP-/- bone marrow with wild-type, phosphatase-dead, C-terminal truncations, and NPXY mutant SHIP constructs; PIP3 measurement; calcium entry; degranulation assays Blood High 11222379
2003 SHIP-1 is tyrosine-phosphorylated after M-CSF stimulation in a Src family kinase-dependent manner and binds Lyn via its SH2 domain (independently of Lyn kinase activity); SHIP-1 negatively regulates M-CSF-induced Akt activation and NF-κB-dependent transcription, with Lyn stabilizing SHIP-1 at the membrane. GST-SH2 fusion protein pulldown; co-immunoprecipitation; SHIP-1 overexpression/SH2-domain constructs in THP-1 cells; macrophages from SHIP-1−/− and Lyn−/− mice; Akt phosphorylation assays The Journal of biological chemistry High 12882960
2003 A somatic mutation in SHIP (V684E) within the phosphatase active-site signature motif reduces SHIP catalytic activity, leading to enhanced Akt phosphorylation and leukemic cell growth advantage, supporting SHIP as a tumor suppressor via the PI3K/Akt pathway. In vitro inositol 5-phosphatase assay with mutant SHIP; Akt phosphorylation assays; transfection of SHIP-V684E into K562 cells; proliferation and apoptosis assays Leukemia Medium 12529653
2004 SHIP1 deficiency in mast cells leads to dysregulated FcεRI signaling characterized by prolonged PIP3 synthesis and Ca2+ mobilization, resulting from loss of SHIP phosphorylation and activity; this is dependent on Lyn kinase for SHIP activation in normal cells. Bone marrow-derived mast cells from Lyn−/− mice; PIP3 measurement; Ca2+ mobilization; SHIP tyrosine phosphorylation assays Journal of immunology Medium 15210764
2004 SHIP1 and Lyn act as negative regulators of integrin αIIbβ3 outside-in signaling in platelets; SHIP1 regulates PIP3 accumulation, Ca2+ responses, and platelet spreading, with Lyn-dependent SHIP1 phosphorylation modulating PtdIns(3,4,5)P3 metabolism and fibrinogen adhesion stability. SHIP1 knockout and Lyn knockout murine platelets; PIP3 measurement; calcium flux; platelet spreading and adhesion assays under physiological blood flow The Journal of biological chemistry High 15166241
2004 SHIP1 and SHIP2 interact preferentially with Tec (vs. other Tec family kinases) via the Tec SH3 domain, and SHIP1 inhibits Tec activity and membrane localization by depleting local PtdIns(3,4,5)P3; constitutively membrane-targeted Tec is resistant to SHIP1 inhibition. Co-immunoprecipitation; kinase activity assays; Tec SH3 domain mutants; membrane-targeting chimeras; SHIP phosphatase assays The Journal of biological chemistry High 15492005
2004 SHIP1 negatively regulates monokine-induced IFN-γ production in NK cells; the inhibitory effect requires SHIP1 catalytic activity, as catalytic-dead SHIP1 overexpression does not suppress IFN-γ, and SHIP1−/− mice produce more IFN-γ from NK cells in vivo. SHIP1 overexpression (wild-type vs. catalytic-dead mutant) in CD56bright NK cells; SHIP1-/- mouse NK cells; IFN-γ production assays in vitro and in vivo Blood High 15604218
2004 LPS-induced endotoxin tolerance requires upregulation of SHIP (not SHIP2 or PTEN); this upregulation is mediated by LPS-induced autocrine TGFβ (via MyD88-dependent pathway), and neutralizing TGFβ blocks tolerance. SHIP-/- macrophages and mast cells cannot establish endotoxin tolerance. SHIP-/- bone marrow-derived macrophages and mast cells; LPS tolerance assays; TGFβ neutralizing antibodies; in vivo SHIP+/+ and SHIP-/- mouse models Immunity High 15308103
2006 SHIP1 controls neutrophil polarity and chemotaxis by governing where PtdIns(3,4,5)P3 accumulates; SHIP1-deficient neutrophils show diffuse PtdIns(3,4,5)P3 distribution and fail to form a leading edge, whereas PTEN deficiency does not affect neutrophil chemotaxis. SHIP1-/- mice; transgenic AktPH-GFP biosensor mice for live PtdIns(3,4,5)P3 imaging; time-lapse microscopy of chemotaxing primary neutrophils Nature cell biology High 17173042
2006 SHIP1 negatively regulates osteoclast precursor proliferation via Akt-dependent modulation of D-type cyclins and p27; SHIP1-null BMMs show enhanced M-CSF-induced Akt activation leading to cyclin D upregulation, p27 downregulation, increased Rb phosphorylation, and proliferation. SHIP1-/- bone marrow macrophages; Akt activation assays; cyclin D and p27 protein levels; Rb phosphorylation; BrdU proliferation assays; inflammatory arthritis model Journal of immunology High 17142780
2007 SHIP-1 (YFP chimera) is recruited to forming phagosomes at the leading edge and dissociates earlier than PI3K (p85), restricting its inhibitory activity to early stages of phagocytosis; PTEN does not localize to phagosomes. This differential localization regulates when and where PIP3 accumulates. Live imaging of YFP-SHIP1, YFP-PTEN, and p85-CFP chimeras in macrophages; quantitative analysis of phagosome PH domain biosensors for PIP3 and PI(3,4)P2 Molecular biology of the cell High 17442886
2007 Small-molecule agonists of SHIP1 activate recombinant SHIP1 enzyme in vitro and stimulate SHIP1 activity in intact macrophages and mast cells by binding an allosteric activation domain distinct from the active site; in vivo administration is protective in endotoxemia and anaphylaxis models. In vitro enzyme activity assays with recombinant SHIP1; cellular phosphoinositide measurements in macrophages and mast cells; in vivo mouse models Blood High 17502453
2008 SHIP-1 activity on phagosomal membranes enhances the early oxidative burst by converting PI(3,4,5)P3 to PI(3,4)P2, which activates NADPH oxidase; SHIP-1-deficient macrophages show elevated PI(3,4,5)P3/PI(3,4)P2 ratios on phagosomes and decreased early NADPH oxidase activity, and altered Rab5a/PI(3)P dynamics indicating disrupted phagosome maturation. SHIP-1-deficient macrophages; phagosomal phospholipid measurements; reactive oxygen species imaging; phagosome maturation markers Journal of immunology High 18490750
2008 NTAL decreases the recruitment of SHIP1 by LAT in mast cell FcεRI signaling complexes; LAT provides two SHIP1 binding sites via its distal tyrosines; reduced SHIP1 recruitment leads to increased Akt phosphorylation and enhanced mast cell survival. Co-immunoprecipitation; NTAL-deficient mast cells; LAT tyrosine mutants; Akt phosphorylation and apoptosis assays Journal of immunology Medium 18322174
2009 SHIP1 is a bona fide target of onco-miR-155; elevated miR-155 driven by autocrine TNFα in DLBCL reduces SHIP1 protein expression, promoting B cell lymphoma proliferation; anti-TNFα treatment restores SHIP1 expression and reduces proliferation. miR-155 target validation in DLBCL cells; anti-TNFα treatment (etanercept/infliximab); SHIP1 protein measurement; tumor xenograft models EMBO molecular medicine Medium 19890474
2009 Lyn, PKC-δ, and SHIP-1 form a specific signaling complex downstream of GPVI (but not PAR) in platelets; Lyn-mediated phosphorylation of SHIP-1 at Y1020 and PKC-δ at Y311 occurs preferentially after GPVI stimulation, and this complex negatively regulates GPVI-mediated dense granule secretion. Co-immunoprecipitation; Lyn-/- and PKC-δ-/- murine platelets; SHIP-1 phosphorylation assays; dense granule secretion assays Blood High 19587372
2010 TREM2/DAP12-induced PI3K signaling requires DAP10 for PI3K recruitment, and SHIP1 inhibits this pathway by binding to DAP12 in an SH2 domain-dependent manner, preventing PI3K recruitment to DAP12. Co-immunoprecipitation; SH2-domain mutants of SHIP1; SHIP1 knockdown; TREM2/DAP12/DAP10 reconstitution experiments; PI3K recruitment assays Science signaling High 20484116
2010 PKA phosphorylates SHIP1 at Ser440 within the catalytic domain, increasing SHIP1 enzymatic activity in hematopoietic cells; S440A mutation abolishes PKA-mediated SHIP1 activation and prevents inhibition of Akt downstream of BCR engagement. Mass spectrometry identification of phosphorylation sites; truncation mutants; S440A site-directed mutagenesis; SHIP1 activity assays; Akt phosphorylation by flow cytometry in DT40 B cells The Journal of biological chemistry High 20810657
2010 Concomitant deletion of PTEN and SHIP in B cells results in spontaneous mature B cell lymphoma, demonstrating that SHIP is a tumor suppressor that cooperates with PTEN to suppress B cell malignancy; bPTEN/SHIP-/- B cells show enhanced survival with increased MCL1, decreased Bim, low p27, and high cyclin D3, and proliferate in response to BAFF. B cell-specific conditional PTEN and SHIP double-knockout mice (Cre-lox); tumor analysis; BCL2-family protein expression; cell cycle analysis; BAFF-dependent proliferation assays The Journal of experimental medicine High 20956547
2010 In SHIP1-/- macrophages stimulated via TLR2/TLR4, enhanced PI3K pathway activation (due to SHIP1 loss) leads to reduced cytokine production, consistent with SHIP1's product PI(3,4)P2 promoting signaling differently from its substrate PIP3; Lyn interacts with PI3K downstream of TLR4/TLR2 as a negative regulatory module. SHIP1-/- bone marrow-derived macrophages; Lyn-/- macrophages; cytokine production assays; PI3K inhibitor treatment Journal of immunology Medium 20385881
2011 SHIP1 SH2 domain undergoes intramolecular and intermolecular interaction with the SHIP1 C-terminus, which regulates the association between SHIP1 and the BCR component Ig-α (ITAM); full-length SHIP1 does not interact with phosphorylated Ig-α ITAM peptide in the same manner as the isolated SH2 domain, indicating autoinhibitory regulation. FRET in S2 cells; pulldown with phospho-ITAM peptides; fluorescently labeled SH2 domain membrane translocation assays; BCR mutants with C-terminally truncated Ig-α Biochimica et biophysica acta Medium 22182704
2012 TIGIT/PVR engagement phosphorylates Tyr225 in the ITT-like motif of TIGIT, which recruits Grb2, which in turn recruits SHIP1 to terminate PI3K and MAPK signaling in NK cells, leading to disrupted granule polarization and loss of cytotoxicity; Y225 or N227 mutation or SHIP1 silencing reverses TIGIT-mediated killing inhibition. TIGIT/PVR ligation; phospho-Tyr225 mutants; Grb2/SHIP1 co-immunoprecipitation; SHIP1 siRNA knockdown; granule polarization and cytotoxicity assays Cell death and differentiation High 23154388
2012 CD2AP forms a complex with SHIP1, and this CD2AP/SHIP1 complex associates with Cbl after BDCA2/FcεR1γ cross-linking, inhibiting Cbl E3 ubiquitin ligase activity to prevent ubiquitination and degradation of Syk and FcεR1γ, thereby positively regulating ITAM signaling in pDCs. Immunoprecipitation and mass spectrometry; Cbl ubiquitin ligase activity assays; CD2AP/SHIP1 knockdown; immunofluorescence co-localization at plasma membrane Journal of immunology Medium 22706086
2014 SHIP1 promotes osteoblast development from mesenchymal stem cells by limiting PI3K/Akt/β-catenin/Id2 pathway activation; SHIP1 deficiency in MSCs reduces bone mass and density, and is the primary cause of osteoporotic phenotype in SHIP1 germline KO mice (not osteoclast SHIP1 deficiency). MSC-specific SHIP1 conditional KO mice vs. myeloid/OC-specific KO; bone densitometry; PI3K/Akt/β-catenin/Id2 pathway analysis; SHIP1 inhibitor treatment Stem cells and development Medium 24857423
2014 SHIP1 associates with the death receptor CD95/Fas and its loss promotes extrinsic T cell death via Caspase 8; Caspase 8 inhibitor treatment prevents SHIP1 inhibitor-mediated T cell death and reduces mucosal inflammation in SHIP1-/- mice. Co-immunoprecipitation of SHIP1 with Fas; Caspase 8 inhibitor treatment; CD4CreSHIP1flox/flox conditional KO mice; mucosal inflammation assays Mucosal immunology Medium 24781051
2015 PSTPIP2 interacts with SHIP1 via PSTPIP2 C-terminal tyrosine residues (critical for PEST-phosphatase-independent inhibitory function); SHIP1 binding is important for PSTPIP2-mediated suppression of IL-1β processing in neutrophils, and SHIP1 inhibition enhances IL-1β processing. Co-immunoprecipitation; PSTPIP2 domain mutants; SHIP1 inhibitor treatment; IL-1β processing assays in neutrophils Journal of immunology Medium 26304991
2023 Reduction in INPP5D/SHIP1 activity in human iPSC-derived microglia induces NLRP3 inflammasome formation, Caspase-1 cleavage, and secretion of IL-1β and IL-18; this is associated with disrupted autophagy; pharmacological inhibition of INPP5D recapitulates inflammasome activation, and evidence for INPP5D/NLRP3 inflammasome connection is confirmed in human AD brain tissue. INPP5D disruption in iPSC-derived human microglia; unbiased RNA/protein profiling; targeted pharmacological experiments; CASP1 cleavage and IL-1β/IL-18 secretion assays; multi-analytic human brain tissue analysis Nature communications High 38016942
2022 SHIP1 agonist K306 activates SHIP1 without requiring the C2 domain (unlike previous agonists), suppresses inflammatory cytokines (TNF-α, iNOS) in macrophages and microglia in a SHIP1-dependent manner, and enhances phagolysosomal degradation of synaptosomes and dead neurons by microglia. In vitro SHIP1 enzyme activation assays; SHIP1-deficient macrophage/microglia controls; cytokine assays; in vivo LPS endotoxemia; synaptosome degradation assays iScience Medium 35465359
2022 Inpp5d haplodeficiency in microglia of 5xFAD mice enhances microglial phagocytosis and amyloid beta clearance, perturbs intracellular signaling pathways regulating immune response, and preserves cognitive function; spatial transcriptomics revealed altered synaptic regulation and immune activation pathways. 5xFAD Inpp5d haploinsufficient mice; behavioral cognitive testing; amyloid plaque quantification; spatial transcriptomics; microglial phagocytosis assays Alzheimer's & dementia Medium 36524682
2023 Microglial SHIP-1 deletion in 5xFAD mice substantially enhances microglial recruitment to Aβ plaques, improves plaque encapsulation and Aβ engulfment, alters microglial gene expression toward activation/phagocytosis programs, and protects against plaque-induced neuronal dystrophy. 5xFAD Inpp5dfl/fl Cx3cr1Ert2Cre conditional microglial KO; microglial recruitment quantification; plaque engulfment assays; gene expression analysis; neuronal health markers Alzheimer's & dementia High 37061460
2010 SHIP1 negatively regulates lentiviral gene transfer-demonstrated PI3K/AKT-driven proliferation of AML CD34+ cells; enzymatically inactive SHIP1 (D672A) has no effect, confirming the requirement for phosphatase activity. Lentiviral gene transfer of wild-type vs. catalytic-dead (D672A) SHIP1 into AML patient CD34+ cells; GM-CSF-dependent proliferation assays Gene therapy Medium 19148132
2010 Ikaros binds to the promoter of the INPP5D gene (encoding SHIP) and is required for SHIP expression; Helios deficiency reduces SHIP expression while Ikaros deficiency upregulates it, providing transcriptional co-regulation of SHIP by Ikaros family factors that governs BCR signaling strength. Chromatin immunoprecipitation (ChIP) of Ikaros at INPP5D promoter; Helios-/- and Ikaros-/- DT40 B cell lines; SHIP mRNA/protein quantification; BCR-induced Ca2+ signaling assays European journal of immunology Medium 20602434

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling. Cell 380 9244303
2010 TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. Science signaling 340 20484116
1998 SHIP modulates immune receptor responses by regulating membrane association of Btk. Immunity 285 9586640
2012 Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells. Cell death and differentiation 261 23154388
2006 Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1. Nature cell biology 240 17173042
2004 LPS-induced upregulation of SHIP is essential for endotoxin tolerance. Immunity 234 15308103
2007 Functional selectivity through protean and biased agonism: who steers the ship? Molecular pharmacology 216 17901198
2009 Hepatitis E outbreak on cruise ship. Emerging infectious diseases 196 19891860
2009 Onco-miR-155 targets SHIP1 to promote TNFalpha-dependent growth of B cell lymphomas. EMBO molecular medicine 177 19890474
2010 The engine driving the ship: metabolic steering of cell proliferation and death. Nature reviews. Molecular cell biology 175 20861880
1998 The inositol phosphatase SHIP inhibits Akt/PKB activation in B cells. The Journal of biological chemistry 167 9852043
2007 Small-molecule agonists of SHIP1 inhibit the phosphoinositide 3-kinase pathway in hematopoietic cells. Blood 125 17502453
2010 SHIP1 inhibition increases immunoregulatory capacity and triggers apoptosis of hematopoietic cancer cells. Journal of immunology (Baltimore, Md. : 1950) 115 20200281
2003 Possible dominant-negative mutation of the SHIP gene in acute myeloid leukemia. Leukemia 105 12529653
2011 Induction of endotoxin tolerance in vivo inhibits activation of IRAK4 and increases negative regulators IRAK-M, SHIP-1, and A20. Journal of leukocyte biology 96 21934070
2012 Therapeutic potential of SH2 domain-containing inositol-5'-phosphatase 1 (SHIP1) and SHIP2 inhibition in cancer. Molecular medicine (Cambridge, Mass.) 94 22033675
2004 Dysregulated FcepsilonRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells. Journal of immunology (Baltimore, Md. : 1950) 93 15210764
2010 Inhibitor and activator: dual functions for SHIP in immunity and cancer. Annals of the New York Academy of Sciences 90 21155837
2021 INPP5D expression is associated with risk for Alzheimer's disease and induced by plaque-associated microglia. Neurobiology of disease 87 33631273
2010 Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases. The Journal of experimental medicine 74 20956547
2003 The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity. The Journal of biological chemistry 74 12882960
2004 SHIP1 and Lyn Kinase Negatively Regulate Integrin alpha IIb beta 3 signaling in platelets. The Journal of biological chemistry 73 15166241
2007 Differential association of phosphatidylinositol 3-kinase, SHIP-1, and PTEN with forming phagosomes. Molecular biology of the cell 72 17442886
2003 The role of SHIP in cytokine-induced signaling. Reviews of physiology, biochemistry and pharmacology 68 12692707
2000 Molecular basis of the recruitment of the SH2 domain-containing inositol 5-phosphatases SHIP1 and SHIP2 by fcgamma RIIB. The Journal of biological chemistry 68 11016922
2010 Activation of murine macrophages via TLR2 and TLR4 is negatively regulated by a Lyn/PI3K module and promoted by SHIP1. Journal of immunology (Baltimore, Md. : 1950) 64 20385881
2004 Differential expression of SHIP1 in CD56bright and CD56dim NK cells provides a molecular basis for distinct functional responses to monokine costimulation. Blood 63 15604218
1998 Role of the inositol phosphatase SHIP in B cell receptor-induced Ca2+ oscillatory response. Journal of immunology (Baltimore, Md. : 1950) 63 9820480
2017 MicroRNA-155 promotes the pathogenesis of experimental colitis by repressing SHIP-1 expression. World journal of gastroenterology 62 28246471
2022 Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association 61 36448627
2023 Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer's disease. Molecular neurodegeneration 60 38017562
2010 Role of SHIP in cancer. Experimental hematology 56 21056081
1997 SIP/SHIP inhibits Xenopus oocyte maturation induced by insulin and phosphatidylinositol 3-kinase. Molecular and cellular biology 56 9111325
2023 INPP5D regulates inflammasome activation in human microglia. Nature communications 55 38016942
2018 Targeting SHP-1, 2 and SHIP Pathways: A Novel Strategy for Cancer Treatment? Oncology 55 29925063
2004 The role of SHIP1 in macrophage programming and activation. Biochemical Society transactions 54 15494015
2009 SHIP limits immunoregulatory capacity in the T-cell compartment. Blood 52 19136659
2009 Lyn, PKC-delta, SHIP-1 interactions regulate GPVI-mediated platelet-dense granule secretion. Blood 52 19587372
2007 The role of SHIP in macrophages. Frontiers in bioscience : a journal and virtual library 50 17485263
2022 INPP5D deficiency attenuates amyloid pathology in a mouse model of Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association 48 36524682
2006 SHIP1 negatively regulates proliferation of osteoclast precursors via Akt-dependent alterations in D-type cyclins and p27. Journal of immunology (Baltimore, Md. : 1950) 48 17142780
2000 SHIP1, an SH2 domain containing polyinositol-5-phosphatase, regulates migration through two critical tyrosine residues and forms a novel signaling complex with DOK1 and CRKL. The Journal of biological chemistry 47 11031258
1999 The role of SHIP in growth factor induced signalling. Progress in biophysics and molecular biology 47 10354708
2001 SHIP's C-terminus is essential for its hydrolysis of PIP3 and inhibition of mast cell degranulation. Blood 46 11222379
2013 Discovery and development of small molecule SHIP phosphatase modulators. Medicinal research reviews 45 24302498
2009 SHIP1 is a repressor of mast cell hyperplasia, cytokine production, and allergic inflammation in vivo. Journal of immunology (Baltimore, Md. : 1950) 45 19542434
2000 Bilevel control of B-cell activation by the inositol 5-phosphatase SHIP. Immunological reviews 45 11043768
2003 Role of Src homology 2-containing-inositol 5'-phosphatase (SHIP) in mast cells and macrophages. Biochemical Society transactions 43 12546703
2000 The SH2 inositol 5-phosphatase Ship1 is recruited in an SH2-dependent manner to the erythropoietin receptor. The Journal of biological chemistry 43 10660611
2008 A novel germ cell-specific protein, SHIP1, forms a complex with chromatin remodeling activity during spermatogenesis. The Journal of biological chemistry 41 18849567
2004 SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase. The Journal of biological chemistry 41 15492005
2015 Association between hepatic steatosis and serum liver enzyme levels with atrial fibrillation in the general population: The Study of Health in Pomerania (SHIP). Atherosclerosis 40 26722832
2012 CD2AP/SHIP1 complex positively regulates plasmacytoid dendritic cell receptor signaling by inhibiting the E3 ubiquitin ligase Cbl. Journal of immunology (Baltimore, Md. : 1950) 40 22706086
2003 Homeostasis and regeneration of the hematopoietic stem cell pool are altered in SHIP-deficient mice. Blood 40 12855581
2009 Differential roles for the inositol phosphatase SHIP in the regulation of macrophages and lymphocytes. Immunologic research 39 18989630
2008 SHIP-1 increases early oxidative burst and regulates phagosome maturation in macrophages. Journal of immunology (Baltimore, Md. : 1950) 39 18490750
2004 Mutation analysis of SHIP gene in acute leukemia. Zhongguo shi yan xue ye xue za zhi 39 15363123
2013 Role of SHIP1 in cancer and mucosal inflammation. Annals of the New York Academy of Sciences 38 23551094
2017 INPP5D mRNA Expression and Cognitive Decline in Japanese Alzheimer's Disease Subjects. Journal of Alzheimer's disease : JAD 37 28482637
2020 Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer. Cancers 36 33291556
2019 Triptolide Inhibits Preformed Fibril-Induced Microglial Activation by Targeting the MicroRNA155-5p/SHIP1 Pathway. Oxidative medicine and cellular longevity 35 31182996
2019 Targeted genetic analysis of cerebral blood flow imaging phenotypes implicates the INPP5D gene. Neurobiology of aging 34 31319229
2019 SHIP-1, a target of miR-155, regulates endothelial cell responses in lung fibrosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34 31907997
2011 Enzymatic and non-enzymatic activities of SHIP-1 in signal transduction and cancer. Biochemical pharmacology 34 21672530
2023 The Alzheimer's disease risk factor INPP5D restricts neuroprotective microglial responses in amyloid beta-mediated pathology. Alzheimer's & dementia : the journal of the Alzheimer's Association 32 37061460
2021 Targeting SHIP1 and SHIP2 in Cancer. Cancers 31 33672717
2015 SHIP1 intrinsically regulates NK cell signaling and education, resulting in tolerance of an MHC class I-mismatched bone marrow graft in mice. Journal of immunology (Baltimore, Md. : 1950) 31 25687756
2015 B cell expression of the SH2-containing inositol 5-phosphatase (SHIP-1) is required to establish anergy to high affinity, proteinacious autoantigens. Journal of autoimmunity 31 26152931
2014 Impaired T-cell survival promotes mucosal inflammatory disease in SHIP1-deficient mice. Mucosal immunology 31 24781051
2020 Small molecule targeting of SHIP1 and SHIP2. Biochemical Society transactions 29 32049315
2017 Do Genetic Markers of Inflammation Modify the Relationship between Periodontitis and Nonalcoholic Fatty Liver Disease? Findings from the SHIP Study. Journal of dental research 29 28732187
2015 Activity of SHIP, Which Prevents Expression of Interleukin 1β, Is Reduced in Patients With Crohn's Disease. Gastroenterology 29 26481854
2010 Concerted action of Helios and Ikaros controls the expression of the inositol 5-phosphatase SHIP. European journal of immunology 29 20602434
2015 PSTPIP2, a Protein Associated with Autoinflammatory Disease, Interacts with Inhibitory Enzymes SHIP1 and Csk. Journal of immunology (Baltimore, Md. : 1950) 28 26304991
2012 Lineage extrinsic and intrinsic control of immunoregulatory cell numbers by SHIP. European journal of immunology 28 22535653
2021 Bortezomib Sustains T Cell Function by Inducing miR-155-Mediated Downregulation of SOCS1 and SHIP1. Frontiers in immunology 27 33717088
2013 Biodegradation of phenanthrene in bioaugmented microcosm by consortium ASP developed from coastal sediment of Alang-Sosiya ship breaking yard. Marine pollution bulletin 26 23906474
2009 Reduced proliferation of CD34(+) cells from patients with acute myeloid leukemia after gene transfer of INPP5D. Gene therapy 25 19148132
2018 SHIP1 Deficiency in Inflammatory Bowel Disease Is Associated With Severe Crohn's Disease and Peripheral T Cell Reduction. Frontiers in immunology 24 29872435
2012 Mouse natural killer cell development and maturation are differentially regulated by SHIP-1. Blood 24 23034281
2008 Non-T cell activation linker promotes mast cell survival by dampening the recruitment of SHIP1 by linker for activation of T cells. Journal of immunology (Baltimore, Md. : 1950) 24 18322174
2020 SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt-STAT5-Trib1 Circuit in Pseudomonas aeruginosa Infection. Frontiers in immunology 23 32256487
2017 IVIG activates FcγRIIB-SHIP1-PIP3 Pathway to stabilize mast cells and suppress inflammation after ICH in mice. Scientific reports 23 29138419
2014 TLR signaling that induces weak inflammatory response and SHIP1 enhances osteogenic functions. Bone research 23 26273527
2011 CIN85 interacting proteins in B cells-specific role for SHIP-1. Molecular & cellular proteomics : MCP 23 21725061
2014 SHIP1 regulates MSC numbers and their osteolineage commitment by limiting induction of the PI3K/Akt/β-catenin/Id2 axis. Stem cells and development 22 24857423
2022 Apigenin Targets MicroRNA-155, Enhances SHIP-1 Expression, and Augments Anti-Tumor Responses in Pancreatic Cancer. Cancers 21 35892872
2013 How does SHIP1/2 balance PtdIns(3,4)P2 and does it signal independently of its phosphatase activity? BioEssays : news and reviews in molecular, cellular and developmental biology 21 23650141
2010 A key role for the phosphorylation of Ser440 by the cyclic AMP-dependent protein kinase in regulating the activity of the Src homology 2 domain-containing Inositol 5'-phosphatase (SHIP1). The Journal of biological chemistry 21 20810657
2022 Discovery of a novel SHIP1 agonist that promotes degradation of lipid-laden phagocytic cargo by microglia. iScience 20 35465359
2009 Fine tuning T lymphocytes: a role for the lipid phosphatase SHIP-1. Biochimica et biophysica acta 20 19782768
2019 Retrospective eDNA assessment of potentially harmful algae in historical ship ballast tank and marine port sediments. Molecular ecology 19 30793442
2018 Effects of guluronic acid (G2013) on SHIP1, SOCS1 induction and related molecules in TLR4 signaling pathway. International immunopharmacology 19 29310108
2017 SHIP1, but not an AML-derived SHIP1 mutant, suppresses myeloid leukemia growth in a xenotransplantation mouse model. Gene therapy 19 29143813
2013 Role of SHIP1 in bone biology. Annals of the New York Academy of Sciences 19 23551095
2011 The SH2-domain of SHIP1 interacts with the SHIP1 C-terminus: impact on SHIP1/Ig-α interaction. Biochimica et biophysica acta 19 22182704
2023 CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression. Frontiers in immunology 18 36923408
2019 Regulation of hematopoietic cell signaling by SHIP-1 inositol phosphatase: growth factors and beyond. Growth factors (Chur, Switzerland) 18 30764683
2016 Overexpression of JARID1B promotes differentiation via SHIP1/AKT signaling in human hypopharyngeal squamous cell carcinoma. Cell death & disease 18 27584795
2015 SHIP1-expressing mesenchymal stem cells regulate hematopoietic stem cell homeostasis and lineage commitment during aging. Stem cells and development 18 25525673