Affinage

SH2B3

SH2B adapter protein 3 · UniProt Q9UQQ2

Length
575 aa
Mass
63.2 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 43 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

SH2B3 (LNK) is an intracellular adaptor protein that acts as a broad negative regulator of cytokine receptor and receptor tyrosine kinase signaling across hematopoietic, endothelial, immune, vascular, and neural cell types, dampening proliferative and inflammatory outputs downstream of these receptors (PMID:12070287, PMID:15705783, PMID:23908464). Its SH2 domain is the essential effector module: it binds directly to specific phosphotyrosine motifs on activated JAK2 and EPOR (PMID:18618018, PMID:34671038), JAK3 (PMID:26974155), c-Kit pTyr568 (PMID:18753636, PMID:18588518), MPL (PMID:17693582), FLT3/FLT3-ITD at pTyr572/591/919 (PMID:22942183), PDGFRs and the FIP1L1-PDGFRA fusion (PMID:21310211), and the phosphatase SHP2 (PMID:24297922), thereby attenuating downstream STAT5/STAT3, PI3K/AKT, and MAPK/ERK signaling (PMID:15337790, PMID:15705783). Crystal structures of the LNK SH2 domain bound to phospho-JAK2 and phospho-EPOR motifs reveal a canonical SH2 fold with an additional N-terminal helix, with binding specificity conferred by the residues at the +1 and +3 positions relative to the phosphotyrosine (PMID:34671038). LNK function is itself tuned by phosphorylation: GSK3- and PKA-phosphorylated serine sites recruit 14-3-3 proteins that compete with JAK2 and sequester LNK in the cytoplasm, relieving its inhibition of signaling (PMID:22546852). Through these activities LNK restrains hematopoietic stem cell self-renewal and progenitor expansion in a thrombopoietin/MPL-dependent manner (PMID:16882979, PMID:17284614, PMID:18618018) and constrains B-lineage and myeloid output (PMID:11114373, PMID:12070287). Loss or mutation of LNK augments JAK-STAT signaling and drives disease: it accelerates oncogenic JAK2-induced myeloproliferative neoplasms and cooperates with tumor suppressor loss to produce B-ALL (PMID:20458146, PMID:23908464, PMID:26974155), and patient-derived PH- and SH2-domain mutations impair target binding and signaling inhibition (PMID:20404132, PMID:34671038). The R262W (rs3184504) risk variant is a loss-of-function allele that enhances cytokine-driven T-cell responses and predisposes to hypertension and renal injury (PMID:36169218), and hematopoietic LNK deficiency promotes vascular inflammation, atherosclerosis, and arterial thrombosis through NETosis/EETosis mechanisms (PMID:25664851, PMID:34846914, PMID:38096361).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 Medium

    Established LNK as a tyrosine-phosphorylated adaptor coupling receptor activation to downstream signaling enzymes, the first hint of its scaffolding role.

    Evidence Co-immunoprecipitation of LNK with PLC-γ1, PI3K, and Grb2 in activated T lymphocytes

    PMID:8524815

    Open questions at the time
    • Direct vs. indirect nature of associations not resolved
    • No receptor target identified
    • Functional consequence of associations untested
  2. 1997 Medium

    Redirected attention from antigen receptors to other receptor systems by showing LNK is not rate-limiting in TCR signaling despite TCR-induced phosphorylation.

    Evidence Transgenic thymocyte overexpression with T cell activation assays in mice

    PMID:9169414

    Open questions at the time
    • Did not identify the relevant non-antigen receptors
    • Loss-of-function not yet tested
  3. 2000 High

    Genetic knockout defined LNK's core physiological function as a negative regulator of hematopoietic cell production downstream of c-Kit, moving beyond correlative biochemistry.

    Evidence Lnk knockout mice with B-cell precursor expansion and SCF hypersensitivity; parallel TCR ζ-chain/p56lck association and NF-AT reporter studies

    PMID:10799879 PMID:11114373

    Open questions at the time
    • Direct receptor-binding mechanism not yet shown
    • Domain requirements undefined
  4. 2002 High

    Broadened LNK's negative regulatory scope across multiple cytokines and mapped its action to specific receptors and effectors, defining it as a multi-pathway brake on progenitor signaling.

    Evidence Lnk knockout progenitor cytokine hypersensitivity (IL-3, IL-7, SCF) and c-Kit association with selective Gab2/MAPK suppression

    PMID:11805142 PMID:12070287

    Open questions at the time
    • Direct phosphotyrosine binding sites not yet mapped
    • SH2 domain requirement not yet isolated
  5. 2004 High

    Isolated the SH2 domain as the essential inhibitory module and the C-terminal tyrosine/PH domain as dispensable, defining the structural logic of LNK inhibition of TPO/MPL signaling.

    Evidence Domain-mutant overexpression and knockout signaling analysis (STAT3/5, Akt, MAPK) in megakaryocytic cells

    PMID:15337790

    Open questions at the time
    • Direct phosphotyrosine target of the SH2 domain not yet identified
    • PH domain contribution not fully resolved
  6. 2005 High

    Pinpointed JAK2 as the proximal target in EPOR signaling, showing LNK attenuates JAK2 activation through its SH2 domain.

    Evidence SH2-mutant analysis in EpoR cells and primary erythroblasts with JAK2/EpoR/STAT5/Akt/MAPK phospho-readouts

    PMID:15705783

    Open questions at the time
    • Direct LNK–JAK2 binding not yet demonstrated biochemically
    • Phosphotyrosine motif unmapped
  7. 2006 High

    Genetic epistasis established that LNK's control of HSC expansion operates specifically through the thrombopoietin axis, linking the molecular brake to a stem-cell-level phenotype.

    Evidence Lnk-/-Thpo-/- double knockout HSC quantification and competitive repopulation; endothelial TNF-α/VCAM-1 studies

    PMID:16644735 PMID:16882979

    Open questions at the time
    • Whether LNK acts directly on MPL or on JAK2 not yet distinguished
    • Endothelial mechanism distinct from hematopoietic
  8. 2007 High

    Mapped LNK action to MPL/STAT5 in HSC self-renewal and showed it directly engages activated MPL including the oncogenic W515L mutant, foreshadowing its tumor-suppressive role.

    Evidence Single-cell HSC assays, transplantation, and Co-IP/colocalization of LNK with MPL and MPLW515L

    PMID:17284614 PMID:17693582

    Open questions at the time
    • Oncogenic mutants more susceptible to LNK — mechanism unexplained
    • Direct phosphotyrosine site on MPL/JAK2 not defined
  9. 2008 High

    Demonstrated direct SH2-mediated binding of LNK to specific phosphotyrosines — JAK2 pY residues and c-Kit pTyr568 — establishing the molecular interaction underlying its inhibition, and showed an oncogenic JAK2 mutant uncoupled from LNK drives worse disease.

    Evidence Co-IP and genetic epistasis for JAK2 (Lnk-/-×Mpl-/-, binding-deficient JAK2 mutant); GST pull-downs with Y568F mutagenesis and peptide competition for c-Kit; platelet integrin/Fyn studies

    PMID:18588518 PMID:18618018 PMID:18753636 PMID:20038804

    Open questions at the time
    • Structural basis of phosphotyrosine recognition not yet resolved
    • Generality of motif across receptors untested
  10. 2010 High

    Established LNK as a genuine tumor suppressor restraining oncogenic JAK2 and revealed patient-derived PH/SH2 mutations as loss-of-function lesions, while extending LNK binding to additional RTKs.

    Evidence Bone marrow transplantation with Lnk-uncoupled JAK2 mutants, patient mutant reconstitution in BaF3-MPL cells, c-Fms Co-IP, R262W genotype-stratified NOD2 assays

    PMID:20404132 PMID:20458146 PMID:20560212 PMID:20571037

    Open questions at the time
    • Quantitative binding effects of mutations not measured
    • R262W mechanism remained correlative at this stage
  11. 2011 Medium

    Extended LNK's negative regulatory reach to PDGFRs, TrkA, focal adhesion machinery, and neural progenitors, defining it as a broadly acting adaptor across cell lineages.

    Evidence SH2-mutant Co-IP for PDGFR/FIP1L1-PDGFRA, TrkA Co-IP and neurite assays, focal-adhesion Co-IP (ILK, alpha-parvin), NSPC stroke model with IGF-1/AKT readout

    PMID:21310211 PMID:22028877 PMID:22441983 PMID:22496561

    Open questions at the time
    • Several interactions rest on single-lab Co-IP
    • Direct vs. indirect binding to focal adhesion partners unresolved
  12. 2012 High

    Identified the regulatory switch controlling LNK itself: 14-3-3 binding at GSK3/PKA-phosphorylated serines competes with JAK2 and sequesters LNK from the membrane, providing feedback release of inhibition.

    Evidence Co-IP, GSK3/PKA kinase assays, subcellular fractionation, serine-site mutagenesis, and bone marrow transplantation

    PMID:22546852

    Open questions at the time
    • Physiological stimuli driving GSK3/PKA phosphorylation of LNK undefined
    • Quantitative competition kinetics not measured
  13. 2013 High

    Cemented LNK as a leukemia suppressor whose loss synergizes with NOTCH1 and tumor-suppressor lesions to drive ALL, and mapped SHP2/PTPN11 as an SH2 target in IL-11 signaling.

    Evidence Lnk-/- combined tumor-suppressor mouse models with transplantation and expression profiling; SHP-2/Grb2 Co-IP in HSPCs; PH-mutant binding panels

    PMID:23590807 PMID:23908464 PMID:24297922

    Open questions at the time
    • Mild PH-mutant phenotypes left their disease contribution uncertain
    • SHP2 binding motif not crystallographically resolved
  14. 2016 Medium

    Defined JAK3/IL-7 as an additional direct SH2 target in B-lineage homeostasis and showed LNK-deficient leukemias are JAK-inhibitor sensitive, linking mechanism to therapy, while clarifying the R262W variant as a quantitative loss-of-function allele driving thrombosis-relevant MPL signaling.

    Evidence Phospho-JAK3 Co-IP and JAK inhibitor treatment of Lnk-/-Tp53-/- leukemias; human cord blood HSC and mouse platelet/SHIP-1 studies of R262W

    PMID:26974155 PMID:27430239

    Open questions at the time
    • Direct JAK3 binding rests on single Co-IP
    • Synergy with hypercholesterolemia mechanistically incomplete
  15. 2018 High

    Revealed non-canonical and tissue-specific roles: LNK loss stabilizes stalled replication forks via JAK2 signaling in Fanconi anemia HSCs and controls adipose immune homeostasis and glucose tolerance through IL-15-dependent innate lymphoid cells.

    Evidence Lnk-/-Fancd2-/- DNA fiber assays and transplantation; Lnk-/-×Il15-/- double knockout, ILC depletion, and JAK inhibitor glucose tolerance tests

    PMID:30110639 PMID:30254368

    Open questions at the time
    • Mechanistic link between JAK2 signaling and fork stability incompletely defined
    • Cell-intrinsic vs. extrinsic ILC effects partially resolved
  16. 2021 High

    Provided the structural basis for SH2 phosphotyrosine recognition and motif specificity, and defined a NETosis/oxidized-phospholipid mechanism by which hematopoietic LNK deficiency drives atherothrombosis.

    Evidence X-ray crystallography of LNK-SH2 bound to phospho-JAK2 and phospho-EPOR with mutagenesis; Lnk-/-PAD4-/- thrombosis models, E06-scFv rescue, and human iPSC LNK(TT) cells

    PMID:34671038 PMID:34846914

    Open questions at the time
    • Structures limited to two motifs; binding to other receptors inferred
    • PH-domain contribution to membrane targeting not structurally resolved
  17. 2022 High

    Demonstrated with a precise CRISPR knock-in that the human R262W variant is a hypomorph enhancing IL-12/STAT4 signaling and IFN-γ production in CD8+ T cells, causally driving hypertension, and extended LNK's JAK2/SHP2-dependent suppression to solid tumors.

    Evidence Arg/Arg vs. Trp/Trp knock-in mice with angiotensin II infusion, Stat4 phospho-readout, and BP telemetry; SH2B3 Co-IP with JAK2/SHP2 and signaling assays in lung cancer cells

    PMID:35589677 PMID:36169218

    Open questions at the time
    • Solid-tumor function rests on single-lab Co-IP and overexpression
    • Cell types beyond CD8+ T cells in the variant phenotype not fully dissected
  18. 2024 High

    Established a cell-type-specific eosinophil pathway, showing eosinophil-intrinsic LNK loss elevates JAK/STAT signaling and drives EETosis-dependent arterial thrombosis, validated in human iPSC-derived cells.

    Evidence Eosinophil-specific conditional Lnk knockout, eosinophil depletion, DNase I rescue, and human iPSC-derived LNK(TT) eosinophil assays

    PMID:38096361

    Open questions at the time
    • Specific receptor driving eosinophil JAK/STAT hyperactivation not defined
    • Relative contribution of eosinophils vs. neutrophils/platelets to thrombosis not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LNK's full domain architecture (PH-mediated membrane targeting, interdomain regions, and SH2) is integrated into a single regulated signaling complex on intact receptors, and the structural basis for binding receptors beyond JAK2/EPOR, remains incompletely defined.
  • No full-length LNK structure
  • PH domain ligand/membrane interaction unresolved
  • Stoichiometry and dynamics of LNK assembly on activated receptors unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-109582 Hemostasis 3 R-HSA-162582 Signal Transduction 3
Partners
EPORFLT3JAK2JAK3KITMPLPDGFRAPTPN11

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 LNK (Lnk) becomes tyrosine phosphorylated upon T-cell receptor and CD4 crosslinking, and co-immunoprecipitates with phospholipase C-γ1, phosphatidylinositol 3-kinase, and Grb2 in activated T lymphocytes, linking TCR activation signals to these downstream pathways. Co-immunoprecipitation from activated T lymphocytes Proceedings of the National Academy of Sciences of the United States of America Medium 8524815
1997 Mouse Lnk is tyrosine phosphorylated during T cell activation, but transgenic overexpression in thymocytes demonstrated it plays no limiting role in TCR signaling, suggesting Lnk participates in signaling from receptors other than antigen receptors. Transgenic mouse overexpression, T cell activation assays The Journal of biological chemistry Medium 9169414
2000 Human LNK is localized at the juxtanuclear compartment and plasma membrane; it is tyrosine phosphorylated by p56lck, which then binds to phospho-LNK through its SH2 domain; LNK associates with tyrosine-phosphorylated TCR zeta-chain via its SH2 domain; overexpression of LNK in Jurkat cells inhibits anti-CD3-mediated NF-AT activation. Confocal fluorescence microscopy (GFP fusion), co-immunoprecipitation in COS cells, NF-AT luciferase reporter assay in Jurkat cells Journal of immunology Medium 10799879
2000 LNK deficiency in mice causes expansion of B lineage cells and hypersensitivity of pro-B cell precursors to SCF (c-Kit ligand), establishing LNK as a negative regulator of B cell production downstream of c-Kit signaling. Lnk knockout mouse generation, bone marrow analysis, B cell precursor culture with SCF Immunity High 11114373
2000 Human LNK binds to the C-terminal segment (repeats 19-23C, residues 2006-2454) of actin-binding protein ABP-280 (filamin A) via a 56-amino acid interdomain region between its PH and SH2 domains; this interaction was confirmed by co-immunoprecipitation of endogenous proteins in Jurkat cells and co-localization at plasma membrane and juxtanuclear region. Yeast two-hybrid screen, co-immunoprecipitation, confocal immunofluorescence Molecular immunology Medium 11163396
2002 Lnk-deficient mice display expanded hematopoietic progenitors with hypersensitivity to multiple cytokines including IL-3, IL-7, and stem cell factor, and Lnk inactivation causes abnormal modulation of IL-3 and SCF-mediated signaling pathways; Lnk is highly expressed in multipotent cells and committed erythroid, megakaryocyte, and myeloid precursors. Lnk knockout mouse generation, in vitro proliferation assays, cytokine signaling (Western blot), expression profiling The Journal of experimental medicine High 12070287
2002 Lnk is phosphorylated by and associates with c-Kit following SCF stimulation; Lnk deficiency enhances c-Kit-mediated signaling and selectively inhibits phosphorylation of Gab2 and activation of the MAPK cascade downstream of c-Kit. Co-immunoprecipitation, Western blot signaling analysis in Lnk-/- hematopoietic progenitors The Journal of experimental medicine Medium 11805142
2004 Lnk overexpression negatively regulates Tpo-mediated megakaryocyte proliferation and endomitosis; Lnk deficiency causes enhanced STAT3, STAT5, Akt, and MAPK signaling in response to Tpo; the SH2 domain of Lnk is essential for its inhibitory function, whereas the conserved C-terminal tyrosine is dispensable and the PH domain contributes but is not essential. Lnk overexpression and knockout in hematopoietic cell lines and primary cells, Western blot signaling analysis, domain mutant analysis The Journal of experimental medicine High 15337790
2005 Lnk negatively modulates EpoR signaling by attenuating JAK2 activation; wild-type Lnk becomes tyrosine phosphorylated following Epo administration and inhibits EpoR phosphorylation; the Lnk SH2 domain is essential for inhibitory function, blocking STAT5, Akt, and MAPK pathways in primary erythroblasts; the conserved C-terminal tyrosine and PH domain are not critical for this inhibition. Lnk overexpression in 32D/EpoR cells and primary fetal liver erythroblasts, Western blot for JAK2/EpoR/STAT5/Akt/MAPK phosphorylation, SH2 domain mutant analysis Blood High 15705783
2006 Lnk regulates postnatal HSC expansion antagonistically to thrombopoietin; Lnk-/- HSCs display enhanced THPO responsiveness and their postnatal expansion is completely dependent on THPO, as Lnk-/-Thpo-/- double knockout mice have 65-fold fewer LT-HSCs than Lnk-/- mice. Genetic double knockout (Lnk-/-Thpo-/-), HSC quantification, competitive repopulation Genes & development High 16882979
2006 In endothelial cells, Lnk down-regulates TNF-α-induced VCAM-1 and E-selectin expression by activating PI3K/Akt signaling and inhibiting ERK1/2 phosphorylation, without affecting NF-κB p65 phosphorylation/translocation or IκBα degradation; endothelial nitric oxide synthase and HO-1 are identified as downstream targets of Lnk-mediated PI3K/Akt activation. Lnk overexpression in endothelial cells, Western blot for VCAM-1/E-selectin/NF-κB/Akt/ERK/p38/JNK, PI3K inhibitor treatment The Journal of biological chemistry Medium 16644735
2007 Lnk negatively regulates the activating MPL mutation MPLW515L; Lnk associates with activated wild-type MPL and MPLW515L at the plasma membrane; the Lnk SH2 domain is essential for binding and down-regulation; MPLW515L-expressing cells are more susceptible to Lnk inhibitory function than MPL wild-type cells; Lnk is tyrosine phosphorylated following TPO stimulation. Co-immunoprecipitation, confocal colocalization, overexpression/knockdown in Ba/F3-MPLW515L and UT7-MPLW515L cells, proliferation assays, Western blot Blood Medium 17693582
2007 Lnk negatively regulates HSC self-renewal specifically through the TPO/Mpl pathway; Lnk-/- HSCs show enhanced TPO-mediated STAT5 activation (but not p38 inactivation in WT HSCs), and symmetrical self-renewal division is efficiently induced by TPO+SCF only in Lnk-deficient HSCs. Single-cell cultures, competitive repopulation, single-cell transplantation, single-cell immunostaining for p38/STAT5/Akt Proceedings of the National Academy of Sciences of the United States of America High 17284614
2008 Lnk directly binds to phosphorylated tyrosine residues in JAK2 following TPO stimulation; Lnk controls HSC quiescence and self-renewal predominantly through Mpl signaling; the JAK2 V617F mutant retains the ability to bind Lnk; an activated JAK2 mutant unable to bind Lnk causes greater myeloid expansion and accelerated myelofibrosis. Co-immunoprecipitation (biochemical binding), genetic epistasis (Lnk-/- × Mpl-/- mice), bone marrow transplantation, 5-FU treatment, cell cycle analysis The Journal of clinical investigation High 18618018
2008 The Lnk SH2 domain binds directly and preferentially to phosphorylated tyrosine 567 in the c-Kit juxtamembrane domain; this binding is abolished by Y568F point mutation (rat c-Kit numbering Y567) and competed by phosphopeptides; Lnk down-regulates SCF-induced MAPK and JNK signaling but not PI3K signaling in mast cells, and inhibits SCF-dependent migration via Rac and p38 MAPK. GST pull-down with c-Kit domain constructs, co-immunoprecipitation with Y568F mutant, Lnk-/- bone marrow mast cells reconstituted with Lnk mutants, proliferation/migration assays, Western blot Blood High 18753636
2008 Lnk associates with c-Kit phospho-Tyr568 in the juxtamembrane domain; binding is abolished by the Y568F mutation and competed by phospho-Tyr568 peptides; Lnk binds directly to c-Kit without requiring other interacting partners, as shown by pull-down with GST-fusion proteins. GST pull-down with c-Kit domain constructs, co-immunoprecipitation with Y568F mutant c-Kit, peptide competition assay The Biochemical journal High 18588518
2008 Lnk regulates integrin alphaIIbbeta3 outside-in signaling in platelets; Lnk-/- platelets show reduced spreading on fibrinogen, reduced clot retraction, reduced tyrosine phosphorylation of the beta3 integrin subunit, and reduced binding of Fyn to integrin alphaIIbbeta3, leading to impaired thrombus stabilization in vivo. In vivo thrombosis models (FeCl3 and laser injury with live imaging), platelet spreading assay, clot retraction assay, co-immunoprecipitation of Fyn with integrin alphaIIbbeta3, Western blot for beta3 phosphorylation The Journal of clinical investigation High 20038804
2009 Lnk inhibits JAK2V617F constitutive activity; Lnk, through its SH2 and PH domains, interacts with both wild-type JAK2 and JAK2V617F; Lnk is tyrosine phosphorylated by constitutively active JAK2V617F; Lnk-deficient murine bone marrow cells are significantly more sensitive to transformation by JAK2V617F in CFU assays. Co-immunoprecipitation, Ba/F3-EpoR proliferation assay, Lnk-/- bone marrow CFU assay with JAK2V617F, Western blot Journal of leukocyte biology Medium 19293402
2010 Lnk deficiency accelerates and exacerbates oncogenic JAK2-induced myeloproliferative disease; an activated form of JAK2 unable to bind Lnk causes greater myeloid expansion and accelerated myelofibrosis, demonstrating that Lnk directly inhibits oncogenic JAK2 in constraining MPD; Lnk deficiency also cooperates with BCR/ABL (which does not directly interact with Lnk) in CML-like disease development. Bone marrow transplantation with JAK2-activated mutants lacking Lnk binding, Lnk-/- mouse models, genetic double mutant analysis The Journal of clinical investigation High 20458146
2010 Disease-associated LNK mutations (5bp deletion/missense causing truncation, and E208Q missense in PH domain) impair LNK function; BaF3-MPL cells transduced with these LNK mutants display augmented and sustained thrombopoietin-dependent growth and JAK-STAT signaling. Retroviral transduction of LNK mutants in BaF3-MPL cells, proliferation assays, JAK-STAT signaling by phosphoflow/Western blot, primary patient CD34+ progenitor analysis Blood Medium 20404132
2010 Carriers of the SH2B3 rs3184504*A (R262W) risk allele show stronger activation of the NOD2 recognition pathway in response to lipopolysaccharide and muramyl dipeptide, suggesting LNK plays a role in innate immune signaling against bacteria. Ex vivo stimulation of peripheral blood cells from genotyped donors, cytokine/NOD2 pathway activation assays American journal of human genetics Low 20560212
2011 LNK (SH2B3) is expressed in endothelial cells and localizes to focal adhesions (co-distributing with vinculin); LNK inhibition decreases cell spreading while sustained expression increases focal adhesion number; LNK regulates beta1-integrin-mediated Akt and GSK3β signaling; alpha-parvin is a molecular target of LNK responsible for impaired focal adhesion dynamics; ILK is identified as a new molecular partner for LNK, which regulates alpha-parvin expression through ILK interaction. RNA interference, immunofluorescence localization, co-immunoprecipitation identifying ILK and alpha-parvin as partners, cell spreading and migration assays, Western blot FASEB journal Medium 22441983
2011 SH2B3 binds to and inhibits neurite outgrowth by binding to phosphorylated TrkA (NGF receptor) via its SH2 domain; SH2B3 represses NGF-induced PLCγ, MEK-ERK1/2, and PI3K-AKT pathway activation and Egr-1 expression; SH2B3 reduces the interaction between SH2B1β and TrkA, competing with positive-acting family members. Overexpression in PC12 cells and primary cortical neurons, Western blot for PLCγ/ERK/AKT/Egr-1, neurite outgrowth assays, co-immunoprecipitation of TrkA with SH2B3/SH2B1β PloS one Medium 22028877
2012 14-3-3 proteins bind to LNK at two serine phosphorylation sites (phosphorylated by GSK3 and PKA kinases); 14-3-3 binding interferes with the LNK-JAK2 interaction, alleviating LNK inhibition of JAK2 signaling; 14-3-3 binding sequesters LNK in the cytoplasm away from the plasma membrane-proximal JAK2; mutations of these serine residues abrogated 14-3-3 binding and augmented LNK's growth inhibitory function. Co-immunoprecipitation, kinase assays (GSK3/PKA), subcellular fractionation, mutagenesis of LNK serine sites, bone marrow transplantation, cell proliferation assays The Journal of clinical investigation High 22546852
2012 Lnk binds to FLT3 and FLT3-ITD through its SH2 domain; the phosphorylated tyrosines 572, 591, and 919 of FLT3 are involved in direct binding to Lnk; Lnk is phosphorylated by both FL-activated FLT3-WT and constitutively active FLT3-ITD; Lnk suppresses FLT3-WT/ITD-dependent signaling and cell proliferation. Co-immunoprecipitation, SH2 domain mutant analysis, shRNA depletion and overexpression in 32D cells, Lnk-/- primary bone marrow FL stimulation assay Blood Medium 22942183
2013 Loss of SH2B3 increases JAK-STAT signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL; combined loss of Lnk and Tp53 or Ink4a/Arf triggers transplantable precursor B-ALL with gene expression profiles similar to human Ph-like B-ALL. Genetic mouse models (Lnk-/- combined with tumor suppressor knockouts), bone marrow transplantation, gene expression profiling, JAK-STAT signaling Western blot Blood High 23908464
2013 SH2B3 (LNK) PH domain missense mutations from MPN patients show mild loss of function against wild-type JAK2 and JAK2V617F but retain binding capacity for JAK2, 14-3-3, and CBL adaptors; no dominant-negative effect was observed. Co-immunoprecipitation of JAK2/14-3-3/CBL with PH domain mutants, signaling assays in transfected cells British journal of haematology Medium 23590807
2013 Lnk suppresses IL-11 signaling in HSPCs by inhibiting tyrosine phosphorylation of SHP-2/PTPN11 and its association with Grb2, and attenuating Erk MAP kinase activation; SHP-2 contains a binding motif for the Lnk SH2 domain that is phosphorylated in response to IL-11 stimulation. Co-immunoprecipitation of SHP-2/Grb2 with Lnk, Western blot for Erk activation, Lnk-/- HSPC radiation resistance assays, IL-11 stimulation Proceedings of the National Academy of Sciences of the United States of America Medium 24297922
2015 Loss of LNK in hematopoietic cells (established by bone marrow transplantation) is primarily responsible for angiotensin II-induced renal and vascular inflammation and predisposition to hypertension; Ang II infusion increases IFN-γ-producing CD8+ T cells in Lnk-/- mice, and IFN-γ deficiency blunts the hypertensive response. Bone marrow transplantation, angiotensin II infusion model, IFN-γ KO epistasis, flow cytometry for CD8+ T cells, renal/vascular histology The Journal of clinical investigation High 25664851
2016 LNK regulates pro-B progenitor homeostasis by attenuating IL-7-stimulated JAK/STAT5 signaling via a direct interaction with phosphorylated JAK3; combined Lnk and Tp53 deficiency triggers B-ALL sensitive to JAK inhibitors. Co-immunoprecipitation of LNK with phospho-JAK3, JAK inhibitor treatment of Lnk-/-Tp53-/- leukemia transplants, IL-7 hypersensitivity assays, gene expression profiling The Journal of clinical investigation Medium 26974155
2016 LNK R262W (TT genotype) is a loss-of-function variant associated with expanded hematopoietic stem cells and enhanced megakaryopoiesis via increased MPL signaling in human cord blood; in Lnk-deficient mice, platelet LNK deficiency increases MPL signaling and AKT activation; hypercholesterolemia acts synergistically with LNK deficiency via SHIP-1 dephosphorylation to further increase AKT and platelet activation. Human cord blood HSC expansion assays, mouse bone marrow transplantation atherosclerosis/thrombosis models, Western blot for Akt/SHIP-1 phosphorylation, platelet activation assays Circulation research Medium 27430239
2018 Lnk deficiency stabilizes stalled replication forks (in a manner partially dependent on alleviating blocks to cytokine-mediated JAK2 signaling) in Fancd2-/- HSCs, reducing replication stress and genomic instability, without impacting ICL repair; this restores HSC function in Fanconi anemia. Genetic double knockout (Lnk-/-Fancd2-/-), DNA fiber assays for fork stability, JAK2 signaling Western blot, HSC reconstitution transplantation, ICL repair assays Nature communications High 30254368
2018 Lnk/Sh2b3 controls adipose tissue homeostasis by negatively regulating IL-15-dependent group 1 innate lymphoid cells (G1-ILCs); Lnk-/- mice have impaired glucose tolerance and accumulation of G1-ILCs in adipose tissue; crossing with Il15-/- mice or depleting G1-ILCs (but not CD8+ T cells) ameliorates glucose intolerance; JAK inhibition improves glucose tolerance in Lnk-/- mice. Lnk-/- × Il15-/- double knockout, cell depletion (anti-NK1.1), JAK inhibitor treatment, flow cytometry, glucose tolerance tests Cell reports High 30110639
2019 LNK suppresses interferon-STAT1 signaling in melanoma; forced LNK expression inhibits IFN-induced STAT1 signaling, cell cycle arrest, and apoptosis; melanoma cells exposed to IFN upregulate LNK expression as a negative feedback mechanism; silencing LNK potentiates IFN-mediated cell killing. LNK overexpression and shRNA/CRISPR-Cas9 knockdown in melanoma cells, Western blot for STAT1 signaling, cell cycle and apoptosis assays, IFN stimulation Nature communications Medium 31110180
2021 Crystal structures of the LNK SH2 domain bound to phosphorylated motifs from JAK2 and EPOR reveal a canonical SH2 fold with an additional N-terminal helix; specificity is conferred by amino acids one and three residues downstream of the phosphotyrosine; disease-associated LNK mutations show impaired target binding in vitro and reduced ability to inhibit signaling. X-ray crystallography (two structures: LNK-SH2/phospho-JAK2 and LNK-SH2/phospho-EPOR), biochemical binding assays, mutagenesis functional signaling assays Nature communications High 34671038
2021 Hematopoietic Lnk deficiency promotes arterial thrombosis via a NETosis mechanism dependent on oxidized phospholipids (OxPL); Lnk-deficient platelets release more OxPL upon thrombin activation and Lnk-deficient neutrophils show increased priming and response to OxPL; PAD4 deficiency completely reversed accelerated thrombosis, and E06-scFv targeting OxPL reversed NETosis, atherosclerosis, and thrombosis. Lnk-/-PAD4-/- double knockout, E06-scFv transgene, carotid artery thrombosis model, OxPL measurement from platelets, NETosis assays, human iPSC-derived LNK(TT) cells Circulation High 34846914
2022 SH2B3 binds to JAK2 and SHP2 to suppress JAK2/STAT3 and SHP2/Grb2/PI3K/AKT signaling pathways in lung cancer cells, inhibiting anoikis resistance, proliferation, migration, invasion, and EMT; TGF-β1 promotes these processes by reducing SH2B3 expression. Co-immunoprecipitation of SH2B3 with JAK2 and SHP2, SH2B3 overexpression in lung cancer lines, Western blot for JAK2/STAT3/Grb2/PI3K/AKT phosphorylation, in vivo xenograft Cell death & disease Medium 35589677
2022 The SH2B3 R262W (Trp/Trp) variant exhibits less negative regulation of IL-12 signaling, resulting in enhanced IL-12-induced Stat4 phosphorylation and IFN-γ production in CD8+ T cells, leading to exacerbated hypertension and renal injury following angiotensin II infusion. CRISPR-Cas9 knock-in mice (Arg/Arg vs. Trp/Trp), angiotensin II infusion model, Stat4 phosphorylation Western blot, IFN-γ ELISA from ex vivo stimulated T cells, blood pressure telemetry Circulation research High 36169218
2024 Eosinophil-specific Lnk deficiency (LnkΔeos mice) causes isolated eosinophilia with increased eosinophil activation and JAK/STAT signaling, accelerating arterial thrombosis through eosinophil extracellular trap (EETosis) formation; DNase I infusion abolishing EETs and NETs reversed the accelerated thrombosis; human iPSC-derived LNK(TT) eosinophils showed increased activation and EETosis. Conditional eosinophil-specific Lnk knockout (eoCre×Lnkf/f), carotid artery thrombosis model, anti-Siglec-F eosinophil depletion, DNase I treatment, human iPSC-derived eosinophil assays, flow cytometry for JAK/STAT signaling Blood High 38096361
2011 Lnk binds to PDGFR-α, PDGFR-β, and the leukemogenic FIP1L1-PDGFRA fusion protein after PDGF exposure; deletion/mutation of the Lnk SH2 domain completely abolishes binding to FIP1L1-PDGFRA (but only partly prevents PDGFRA/B binding); Lnk inhibits PDGF-dependent proliferation and Erk phosphorylation, and suppresses growth of FIP1L1-PDGFRA- and TEL-PDGFRB-transformed 32D cells. Co-immunoprecipitation in 293T cells with SH2 mutants, Ba/F3 and 32D cell proliferation assays, Western blot for pErk Experimental hematology Medium 21310211
2010 Lnk inhibits c-Fms (M-CSFR) signaling; Lnk binds to c-Fms; Lnk deficiency increases M-CSF-induced Akt phosphorylation (augmented and prolonged) while diminishing Erk phosphorylation, enhances ROS production, and inhibits M-CSF-induced macrophage migration. Co-immunoprecipitation of Lnk with c-Fms, Western blot for Akt/Erk in Lnk-/- vs. WT macrophages, clonogenic (M-CFU) assay, ROS production assay, migration assay Journal of leukocyte biology Medium 20571037
2011 LNK is expressed in neural stem and progenitor cells (NSPCs) in adult mouse and human SVZ; Lnk deficiency increases NSPC proliferation after stroke but not in intact brain; Lnk expression after stroke is upregulated through STAT1/3 transcription factors; LNK attenuates IGF-1 signaling by inhibiting AKT phosphorylation, reducing NSPC proliferation. Lnk-/- mouse stroke model, BrdU/EdU incorporation for proliferation, LNK overexpression in NSPC cultures, Western blot for AKT phosphorylation, STAT1/3 ChIP/reporter analysis The Journal of neuroscience Medium 22496561
2011 TPO-stimulated Lnk-deficient HSCs show enhanced Bcl-xL expression compared to normal HSCs; Bcl-xL downregulation by shRNA in Lnk-deficient HSCs reduces their reconstitution capacity; Lnk constrains Bcl-xL expression and thereby controls HSC apoptosis and survival downstream of TPO signaling. Western blot for Bcl-xL in Lnk-/- vs. WT HSCs, shRNA knockdown of Bcl-xL in Lnk-/- HSCs, competitive reconstitution transplantation, irradiation survival assay Experimental hematology Medium 22101255

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood 288 20404132
2002 Cytokine signaling and hematopoietic homeostasis are disrupted in Lnk-deficient mice. The Journal of experimental medicine 199 12070287
2005 Lnk inhibits erythropoiesis and Epo-dependent JAK2 activation and downstream signaling pathways. Blood 191 15705783
2008 Lnk controls mouse hematopoietic stem cell self-renewal and quiescence through direct interactions with JAK2. The Journal of clinical investigation 172 18618018
2010 LNK mutation studies in blast-phase myeloproliferative neoplasms, and in chronic-phase disease with TET2, IDH, JAK2 or MPL mutations. Leukemia 166 20724988
2004 Lnk inhibits Tpo-mpl signaling and Tpo-mediated megakaryocytopoiesis. The Journal of experimental medicine 160 15337790
1995 Cloning and characterization of Lnk, a signal transduction protein that links T-cell receptor activation signal to phospholipase C gamma 1, Grb2, and phosphatidylinositol 3-kinase. Proceedings of the National Academy of Sciences of the United States of America 148 8524815
2010 Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection. American journal of human genetics 144 20560212
2015 Lymphocyte adaptor protein LNK deficiency exacerbates hypertension and end-organ inflammation. The Journal of clinical investigation 136 25664851
2002 Enhanced hematopoiesis by hematopoietic progenitor cells lacking intracellular adaptor protein, Lnk. The Journal of experimental medicine 122 11805142
2007 Lnk negatively regulates self-renewal of hematopoietic stem cells by modifying thrombopoietin-mediated signal transduction. Proceedings of the National Academy of Sciences of the United States of America 119 17284614
2000 Control of B cell production by the adaptor protein lnk. Definition Of a conserved family of signal-modulating proteins. Immunity 119 11114373
2011 The adaptor Lnk (SH2B3): an emerging regulator in vascular cells and a link between immune and inflammatory signaling. Biochemical pharmacology 113 21723852
2010 Lnk constrains myeloproliferative diseases in mice. The Journal of clinical investigation 106 20458146
2006 Cytokines regulate postnatal hematopoietic stem cell expansion: opposing roles of thrombopoietin and LNK. Genes & development 104 16882979
2013 Genetic loss of SH2B3 in acute lymphoblastic leukemia. Blood 102 23908464
2017 The role of LNK/SH2B3 genetic alterations in myeloproliferative neoplasms and other hematological disorders. Leukemia 99 28484264
2000 Cloning and characterization of human Lnk, an adaptor protein with pleckstrin homology and Src homology 2 domains that can inhibit T cell activation. Journal of immunology (Baltimore, Md. : 1950) 90 10799879
2009 Lnk inhibits myeloproliferative disorder-associated JAK2 mutant, JAK2V617F. Journal of leukocyte biology 79 19293402
2021 Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency. Circulation 78 34846914
2010 The autoimmune disease-associated KIF5A, CD226 and SH2B3 gene variants confer susceptibility for multiple sclerosis. Genes and immunity 78 20508602
2022 TGF-β1/SH2B3 axis regulates anoikis resistance and EMT of lung cancer cells by modulating JAK2/STAT3 and SHP2/Grb2 signaling pathways. Cell death & disease 74 35589677
2010 Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk. PLoS genetics 70 20333234
2016 LNK/SH2B3 Loss of Function Promotes Atherosclerosis and Thrombosis. Circulation research 67 27430239
2009 The Drosophila SH2B family adaptor Lnk acts in parallel to chico in the insulin signaling pathway. PLoS genetics 67 19680438
2015 Time-dependent sequestration of RVE8 by LNK proteins shapes the diurnal oscillation of anthocyanin biosynthesis. Proceedings of the National Academy of Sciences of the United States of America 64 25848001
2009 Lnk regulates integrin alphaIIbbeta3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo. The Journal of clinical investigation 64 20038804
1997 Characterization of Lnk. An adaptor protein expressed in lymphocytes. The Journal of biological chemistry 62 9169414
2016 LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors. The Journal of clinical investigation 60 26974155
2007 Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders. Blood 58 17693582
2021 LNK promotes granulosa cell apoptosis in PCOS via negatively regulating insulin-stimulated AKT-FOXO3 pathway. Aging 57 33495419
2014 12q24 locus association with type 1 diabetes: SH2B3 or ATXN2? World journal of diabetes 52 24936253
2006 The adaptor molecule Lnk negatively regulates tumor necrosis factor-alpha-dependent VCAM-1 expression in endothelial cells through inhibition of the ERK1 and -2 pathways. The Journal of biological chemistry 52 16644735
2009 Pivotal role of lnk adaptor protein in endothelial progenitor cell biology for vascular regeneration. Circulation research 51 19325148
2003 Impaired lymphopoiesis and altered B cell subpopulations in mice overexpressing Lnk adaptor protein. Journal of immunology (Baltimore, Md. : 1950) 42 12517931
2008 Lnk adaptor protein down-regulates specific Kit-induced signaling pathways in primary mast cells. Blood 41 18753636
2016 Linking inflammation and hypertension via LNK/SH2B3. Current opinion in nephrology and hypertension 40 26717315
2012 LNK (SH2B3) is a key regulator of integrin signaling in endothelial cells and targets α-parvin to control cell adhesion and migration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 40 22441983
2012 ATXN2 and its neighbouring gene SH2B3 are associated with increased ALS risk in the Turkish population. PloS one 39 22916186
2005 Enhanced engraftment of hematopoietic stem/progenitor cells by the transient inhibition of an adaptor protein, Lnk. Blood 39 16332975
2016 LNK mutations and myeloproliferative disorders. American journal of hematology 38 26660394
2001 Lnk adaptor: novel negative regulator of B cell lymphopoiesis. Science's STKE : signal transduction knowledge environment 38 11752654
2008 Growth and maturation of megakaryocytes is regulated by Lnk/Sh2b3 adaptor protein through crosstalk between cytokine- and integrin-mediated signals. Experimental hematology 37 18456388
2012 Adaptor protein Lnk binds to and inhibits normal and leukemic FLT3. Blood 36 22942183
2012 Role of the adaptor protein LNK in normal and malignant hematopoiesis. Oncogene 35 23045270
2010 Lnk deletion reinforces the function of bone marrow progenitors in promoting neovascularization and astrogliosis following spinal cord injury. Stem cells (Dayton, Ohio) 35 19859984
2000 Molecular cloning of the mouse APS as a member of the Lnk family adaptor proteins. Biochemical and biophysical research communications 33 10872802
2016 Co-existence of IL7R high and SH2B3 low expression distinguishes a novel high-risk acute lymphoblastic leukemia with Ikaros dysfunction. Oncotarget 32 27322554
2011 Octa-arginine mediated delivery of wild-type Lnk protein inhibits TPO-induced M-MOK megakaryoblastic leukemic cell growth by promoting apoptosis. PloS one 32 21853157
2003 Regulation of hematopoietic development in the aorta-gonad-mesonephros region mediated by Lnk adaptor protein. Molecular and cellular biology 32 14612394
2021 The Role of LNK (SH2B3) in the Regulation of JAK-STAT Signalling in Haematopoiesis. Pharmaceuticals (Basel, Switzerland) 31 35056081
2019 SH2B3 inactivation through CN-LOH 12q is uniquely associated with B-cell precursor ALL with iAMP21 or other chromosome 21 gain. Leukemia 30 30816328
2015 SH2B3 Is a Genetic Determinant of Cardiac Inflammation and Fibrosis. Circulation. Cardiovascular genetics 30 25628389
2014 Lnk/Sh2b3 controls the production and function of dendritic cells and regulates the induction of IFN-γ-producing T cells. Journal of immunology (Baltimore, Md. : 1950) 30 25024389
2011 The carriage of the type 1 diabetes-associated R262W variant of human LNK correlates with increased proliferation of peripheral blood monocytes in diabetic patients. Pediatric diabetes 30 20546165
2011 A nonsynonymous LNK polymorphism associated with idiopathic erythrocytosis. American journal of hematology 30 21990094
2022 A Single Nucleotide Polymorphism in SH2B3/LNK Promotes Hypertension Development and Renal Damage. Circulation research 28 36169218
2012 14-3-3 regulates the LNK/JAK2 pathway in mouse hematopoietic stem and progenitor cells. The Journal of clinical investigation 27 22546852
2010 Lnk-dependent axis of SCF-cKit signal for osteogenesis in bone fracture healing. The Journal of experimental medicine 26 20855498
2011 The adaptor protein SH2B3 (Lnk) negatively regulates neurite outgrowth of PC12 cells and cortical neurons. PloS one 25 22028877
2010 Adaptor protein Lnk inhibits c-Fms-mediated macrophage function. Journal of leukocyte biology 25 20571037
2019 LNK suppresses interferon signaling in melanoma. Nature communications 24 31110180
2012 Lnk deficiency partially mitigates hematopoietic stem cell aging. Aging cell 24 22812478
2004 Roles of a conserved family of adaptor proteins, Lnk, SH2-B, and APS, for mast cell development, growth, and functions: APS-deficiency causes augmented degranulation and reduced actin assembly. Biochemical and biophysical research communications 24 14766215
2015 Selective Interference Targeting of Lnk in Umbilical Cord-Derived Late Endothelial Progenitor Cells Improves Vascular Repair, Following Hind Limb Ischemic Injury, via Regulation of JAK2/STAT3 Signaling. Stem cells (Dayton, Ohio) 23 25537795
2023 Modulation of JAK-STAT Signaling by LNK: A Forgotten Oncogenic Pathway in Hormone Receptor-Positive Breast Cancer. International journal of molecular sciences 22 37834225
2018 The LNK Gene Family: At the Crossroad between Light Signaling and the Circadian Clock. Genes 22 30577529
2016 Overexpression of Lnk in the Ovaries Is Involved in Insulin Resistance in Women With Polycystic Ovary Syndrome. Endocrinology 22 27459314
2014 LNK (SH2B3): paradoxical effects in ovarian cancer. Oncogene 22 24704825
2011 Adaptor protein Lnk binds to PDGF receptor and inhibits PDGF-dependent signaling. Experimental hematology 22 21310211
2000 Identification of actin binding protein, ABP-280, as a binding partner of human Lnk adaptor protein. Molecular immunology 22 11163396
2018 Lnk/Sh2b3 Regulates Adipose Inflammation and Glucose Tolerance through Group 1 ILCs. Cell reports 20 30110639
2008 Adaptor protein Lnk associates with Tyr(568) in c-Kit. The Biochemical journal 20 18588518
2018 LNK deficiency promotes acute aortic dissection and rupture. JCI insight 19 30333305
2013 The Lnk/SH2B adaptor provides a fail-safe mechanism to establish the Insulin receptor-Chico interaction. Cell communication and signaling : CCS 19 23590848
2020 LNK deficiency decreases obesity-induced insulin resistance by regulating GLUT4 through the PI3K-Akt-AS160 pathway in adipose tissue. Aging 18 32911464
2019 MicroRNA-29b upregulation improves myocardial fibrosis and cardiac function in myocardial infarction rats through targeting SH2B3. European review for medical and pharmacological sciences 18 31799683
2018 Lnk/Sh2b3 deficiency restores hematopoietic stem cell function and genome integrity in Fancd2 deficient Fanconi anemia. Nature communications 18 30254368
2014 Lnk prevents inflammatory CD8⁺ T-cell proliferation and contributes to intestinal homeostasis. European journal of immunology 18 24536025
2013 Lnk adaptor suppresses radiation resistance and radiation-induced B-cell malignancies by inhibiting IL-11 signaling. Proceedings of the National Academy of Sciences of the United States of America 18 24297922
2011 Gene transfer of the adaptor Lnk (SH2B3) prevents porcine endothelial cell activation and apoptosis: implication for xenograft's cytoprotection. Xenotransplantation 18 21496118
2023 Biallelic deleterious germline SH2B3 variants cause a novel syndrome of myeloproliferation and multi-organ autoimmunity. EJHaem 17 37206266
2018 SH2B3 aberrations enriched in iAMP21 B lymphoblastic leukemia. Cancer genetics 17 30005852
2019 Evidence for a Causal Role of the SH2B3-β2M Axis in Blood Pressure Regulation. Hypertension (Dallas, Tex. : 1979) 16 30624993
2016 The Polymorphisms in LNK Gene Correlated to the Clinical Type of Myeloproliferative Neoplasms. PloS one 16 27111338
2013 SH2B3 (LNK) mutations from myeloproliferative neoplasms patients have mild loss of function against wild type JAK2 and JAK2 V617F. British journal of haematology 16 23590807
2002 Transcriptional up-regulation of the signaling regulatory protein LNK in activated endothelial cells. Transplantation 16 12451278
2022 Farnesyltransferase inhibitor LNK-754 attenuates axonal dystrophy and reduces amyloid pathology in mice. Molecular neurodegeneration 15 35987691
2020 LNK promotes the growth and metastasis of triple negative breast cancer via activating JAK/STAT3 and ERK1/2 pathway. Cancer cell international 15 32322171
2013 Thrombotic antiphospholipid syndrome shows strong haplotypic association with SH2B3-ATXN2 locus. PloS one 15 23844121
2013 SH2B3: a new leukemia predisposition gene. Blood 15 24092923
2012 Adaptor protein LNK is a negative regulator of brain neural stem cell proliferation after stroke. The Journal of neuroscience : the official journal of the Society for Neuroscience 15 22496561
2021 Structural and functional analysis of target recognition by the lymphocyte adaptor protein LNK. Nature communications 14 34671038
2020 The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects. The journals of gerontology. Series A, Biological sciences and medical sciences 14 31428775
2009 Expression of the adaptor protein Lnk in leukemia cells. Experimental hematology 14 19375649
2024 Germline bi-allelic SH2B3/LNK alteration predisposes to a neonatal juvenile myelomonocytic leukemia-like disorder. Haematologica 13 37981895
2024 Hematopoietic and eosinophil-specific LNK(SH2B3) deficiency promotes eosinophilia and arterial thrombosis. Blood 13 38096361
2022 MIR22HG Aggravates Oxygen-Glucose Deprivation and Reoxygenation-Induced Cardiomyocyte Injury through the miR-9-3p/SH2B3 Axis. Cardiovascular therapeutics 13 35692373
2016 Specific disruption of Lnk in murine endothelial progenitor cells promotes dermal wound healing via enhanced vasculogenesis, activation of myofibroblasts, and suppression of inflammatory cell recruitment. Stem cell research & therapy 13 27793180
2011 Homeostasis of hematopoietic stem cells regulated by the myeloproliferative disease associated-gene product Lnk/Sh2b3 via Bcl-xL. Experimental hematology 12 22101255

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