Affinage

LYN

Tyrosine-protein kinase Lyn · UniProt P07948

Length
512 aa
Mass
58.6 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LYN is a Src-family non-receptor tyrosine kinase that physically couples to immunoreceptors and other surface receptors to set the threshold and outcome of their signaling, functioning as both a positive initiator and a negative terminator (PMID:1702903, PMID:9547345, PMID:16272347). In B cells, LYN associates with the antigen receptor (IgM/IgD) and is activated upon receptor cross-linking, where it engages PI3-kinase and drives Ca2+ mobilization through an IP3-independent route downstream of the BCR (PMID:1702903, PMID:8349296, PMID:8137818). Its defining regulatory role is to phosphorylate inhibitory co-receptors and phosphatases that brake immunoreceptor signaling: LYN phosphorylates FcγRIIB and CD22 to recruit SHP-1 and SHIP (PMID:9547345), phosphorylates SHIP1 in platelets and mast cells (PMID:15166241, PMID:15210764), and activates SHP-1 via phosphorylation of Tyr536 and Tyr564 to enforce homeostatic signaling (PMID:20858858, PMID:28811476). Accordingly, loss of LYN produces BCR/FcεRI hyperactivation, defective inhibitory co-receptor phosphorylation, myeloproliferation, and lupus-like autoimmunity, the latter mediated through unrestrained IRF5 activity and an amplified CD11b-Syk-CARD9 axis in dendritic cells (PMID:9547345, PMID:15210764, PMID:27521268, PMID:31594855). Beyond immune cells, LYN propagates signaling from G-CSF, IL-5, erythropoietin, AMPA, and integrin/growth-factor receptors, phosphorylating substrates including Shc, STAT3, band-3, Cbp/PAG, GADD34, FAK, and SgK269/PEAK1 (PMID:7650013, PMID:17146444, PMID:8841404, PMID:11517336, PMID:11823534, PMID:16920712, PMID:24108461, PMID:23378338). LYN activity is tightly controlled: its open-conformation C-lobe binds ACSL3 to license Golgi-to-plasma-membrane export (PMID:20605918), its nuclear accumulation is gated by Crm1-dependent export and kinase-activity-dependent retention (PMID:18817770), it is recruited to membrane rafts in a palmitoylation- and catalysis-dependent manner (PMID:28228554), and its kinase activity is covalently abolished by fumarate-mediated succination at Cys381 (PMID:35710616). Context-specific overactivation drives EMT and metastasis via EPHA2-LYN-TWIST1 and SNAI/Vav-Rac1-PAK1 signaling (PMID:32574556, PMID:28288135), imatinib resistance through Bcl-2 upregulation (PMID:15175350), CBL-mutant PI3K/AKT signaling (PMID:33512474), and flavivirus egress through secretory autophagy (PMID:33060596). Germline constitutively activating LYN mutations cause a human disorder of cutaneous vasculitis and liver fibrosis driven by enhanced neutrophil-endothelial adhesion (PMID:36932076).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1991 High

    Established the founding physical link between LYN and an immunoreceptor, defining it as a BCR-associated kinase rather than a freely diffusing enzyme.

    Evidence Co-immunoprecipitation of Lyn and its kinase activity with membrane IgM from B cell lysates

    PMID:1702903

    Open questions at the time
    • Did not define the structural basis of receptor association
    • No catalytic substrate identified at this stage
  2. 1994 High

    Resolved the division of labor in BCR signaling by placing LYN as a regulator of Ca2+ mobilization through an IP3-independent pathway, distinct from Syk-driven IP3 generation.

    Evidence Lyn-negative and Syk-negative B cell lines with calcium flux and IP3 measurement

    PMID:8137818

    Open questions at the time
    • Molecular identity of the IP3-independent Ca2+ pathway not defined
    • Did not separate positive from negative LYN functions
  3. 1998 High

    Defined LYN's central negative-regulatory function by showing it phosphorylates inhibitory co-receptors FcγRIIB and CD22 to recruit phosphatases and suppress BCR signaling.

    Evidence Lyn-/- mouse B cells with Co-IP, phosphotyrosine blotting, and Ca2+ assays

    PMID:9547345

    Open questions at the time
    • Did not reconcile simultaneous positive and negative roles
    • Phosphosites on co-receptors not exhaustively mapped
  4. 1998 High

    Extended LYN signaling beyond immunoreceptors by demonstrating a non-redundant, kinase-dependent requirement for cytokine (G-CSF) and neurotransmitter (AMPA) receptor signaling.

    Evidence lyn-deficient cell rescue with WT vs kinase-dead Lyn; AMPA receptor Co-IP with dominant-negative Lyn

    PMID:9452436 PMID:9892356

    Open questions at the time
    • Direct substrate in G-CSF mitogenic pathway not fully defined
    • Mechanism of receptor coupling in neurons unresolved
  5. 2001 High

    Identified SH3-domain-mediated substrate selection by showing LYN binds and phosphorylates GADD34 to suppress DNA-damage-induced apoptosis in a kinase-dependent manner.

    Evidence Yeast two-hybrid, GST-SH3 pulldown, Co-IP, in vitro kinase, kinase-dead apoptosis assay

    PMID:11517336

    Open questions at the time
    • In vivo relevance of GADD34 phosphorylation not established
    • Phosphosite on GADD34 not mapped
  6. 2005 Medium

    Reconciled LYN's dual nature by showing stimulation intensity determines whether LYN amplifies or dampens FcεRI signaling, switching between activating association and phosphatase recruitment.

    Evidence WT and Lyn-/- mast cells with FcεRI beta-ITAM mutants and degranulation assays

    PMID:16272347

    Open questions at the time
    • Molecular switch governing the intensity threshold not defined
    • Single-lab cell-based model
  7. 2006 High

    Uncovered a self-limiting feedback circuit in which LYN phosphorylates Cbp/PAG to recruit Csk (rapid inhibition) and SOCS1 (delayed LYN degradation), defining how its own activity is terminated.

    Evidence Co-IP, phosphosite mapping (Tyr314), Csk/SOCS1 recruitment and ubiquitination assays in erythroid cells

    PMID:16920712

    Open questions at the time
    • Quantitative kinetics of the two-phase shutdown not modeled
    • Generality across cell types not tested
  8. 2010 High

    Mapped LYN-driven phosphatase activation to specific SHP-1 tyrosines (Y536, Y564) and showed loss causes constitutive STAT5 activation and CMML-like disease, linking the negative-regulatory role to malignancy.

    Evidence In vitro kinase with phosphosite mutants and lyn-/-;PLC-β3-/- mice

    PMID:20858858

    Open questions at the time
    • Did not address site-specific regulation in non-hematopoietic cells
    • Contribution of PLC-β3 vs LYN loss partially confounded
  9. 2010 High

    Defined the conformational gating of LYN trafficking by showing the open-conformation C-lobe binds ACSL3 to enable Golgi-to-plasma-membrane export, with Csk-induced closure blocking it.

    Evidence Co-IP, ACSL3 KD/OE, live imaging, fractionation, conformational mutants

    PMID:20605918

    Open questions at the time
    • Structural detail of the C-lobe-ACSL3 interface not resolved
    • Signals triggering conformational switching at the Golgi unknown
  10. 2013 High

    Established a LYN function in endothelial barrier integrity by showing LYN phosphorylates FAK to stabilize adherens junctions, with loss increasing vascular permeability in vivo.

    Evidence Co-IP, phosphosite identification, Lyn-/- mice, permeability assays

    PMID:24108461

    Open questions at the time
    • Upstream activator of endothelial LYN not defined
    • Link to the later vasculitis phenotype not made at this stage
  11. 2016 High

    Demonstrated a kinase-independent scaffolding function by showing LYN binds IRF5 to block its ubiquitination/phosphorylation, with Irf5 deletion rescuing autoimmunity in Lyn-/- mice.

    Evidence Co-IP, ubiquitination assay, kinase-inactive mutant, Lyn-/-Irf5+/- mice

    PMID:27521268

    Open questions at the time
    • Structural basis of LYN-IRF5 interaction not defined
    • How kinase-dependent and -independent functions are partitioned unclear
  12. 2017 High

    Resolved how opposing kinases tune the same phosphatase by showing LYN activates SHP-1 (Tyr536) while Fyn inactivates it (Ser591), determining immune homeostasis versus inflammation.

    Evidence In vitro kinase assays, phospho-specific antibodies, Lyn-/- and Fyn-/- mice, SHP-1 phosphomutants

    PMID:28811476

    Open questions at the time
    • Spatial/temporal coordination of LYN vs Fyn on SHP-1 in vivo not resolved
  13. 2020 High

    Defined a mechanotransduction pathway in which matrix stiffness activates EPHA2-LYN, and LYN phosphorylates TWIST1 to release it from G3BP2 and drive EMT and metastasis.

    Evidence Co-IP, phosphorylation assays, genetic KO, mechanically tunable substrates, in vivo metastasis models

    PMID:32574556

    Open questions at the time
    • TWIST1 phosphosite stoichiometry in tumors not quantified
    • Crosstalk with other LYN EMT routes (SNAI) not integrated
  14. 2022 High

    Identified a metabolic control point by showing fumarate covalently succinates LYN at Cys381 to inhibit its kinase activity and suppress B-cell activation.

    Evidence MS succination-site mapping, in vitro kinase assay, FH inhibition and DMF treatment in vitro and in vivo

    PMID:35710616

    Open questions at the time
    • Extent of succination regulation in non-B-cell contexts unknown
    • Reversibility of the modification in vivo not defined
  15. 2023 Medium

    Connected LYN gain-of-function directly to human disease, showing constitutively activating mutations enhance neutrophil-endothelial adhesion causing vasculitis and liver fibrosis, treatable with dasatinib.

    Evidence NGS of patients, patient-derived endothelial cells and neutrophil adhesion/TEM assays, dasatinib treatment

    PMID:36932076

    Open questions at the time
    • Small patient numbers
    • Mechanistic link between LYN activity and ICAM-1/β2-integrin transcription not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LYN's intrinsic conformational state, lipid modification, subcellular trafficking, and metabolic (succination) regulation are integrated to select between its positive and negative signaling outputs in a given cell remains unresolved.
  • No unified model linking conformation, localization, and substrate choice
  • Structural basis of receptor- and substrate-specific recruitment largely undefined
  • In vivo dynamics of the activating/inhibitory switch not directly measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016740 transferase activity 5 GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-109582 Hemostasis 2
Partners
CBP/PAGCD22EPHA2FAKFCGR2BIRF5SHIP1SHP-1

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Lyn protein and its kinase activity co-immunoprecipitate with membrane-bound IgM from B cell detergent lysates, establishing that Lyn is physically associated with the B cell antigen receptor (BCR/IgM). Co-immunoprecipitation from B cell lysates Science High 1702903
1993 Lyn (p56lyn and p53lyn) co-immunoprecipitates with both IgM and IgD from B cell detergent lysates; BCR cross-linking rapidly increases Lyn kinase activity and induces association of Lyn with the p85 subunit of PI3-kinase; HS1 was identified as a downstream substrate of Lyn. Co-immunoprecipitation, in vitro kinase assay Immunological reviews Medium 8349296
1994 In Lyn-deficient B cells, BCR crosslinking produces delayed and slow Ca2+ mobilization despite normal IP3 generation kinetics, whereas Syk mediates IP3 generation; this epistasis places Lyn as regulating Ca2+ mobilization through an IP3-independent pathway downstream of BCR. Lyn-negative and Syk-negative B cell lines, calcium flux assay, IP3 measurement The EMBO journal High 8137818
1995 Activation of the N-formyl peptide chemoattractant receptor (G protein-coupled) in human neutrophils stimulates Lyn kinase, which then associates with and phosphorylates the Shc adapter protein via Shc's SH2 domain; phosphorylated Lyn-Shc complexes associate with PI3-kinase, correlating with PIP3 formation. Co-immunoprecipitation, in vitro kinase assay, phosphotyrosine blotting in human neutrophils The Journal of biological chemistry Medium 7650013
1995 LPS and Taxol rapidly induce autophosphorylation of Lyn (p53 and p56 isoforms) in LPS-responsive macrophages but not in LPS-hyporesponsive C3H/HeJ macrophages; tyrosine phosphatase inhibitors block LPS-induced Lyn autophosphorylation, indicating phosphatases participate in regulating Lyn kinase activity. Immunoprecipitation, in vitro kinase assay, 32P incorporation, LPS-responsive vs. hyporesponsive macrophage comparison Molecular medicine Medium 8521300
1996 Lyn phosphorylates the cytoplasmic domain of band-3 protein in human erythrocytes; the Syk-catalyzed phosphorylation of band-3 is a prerequisite for Lyn membrane association and subsequent Lyn-catalyzed phosphorylation of distinct band-3 tyrosine residues. In vitro kinase assay with isolated erythrocyte membranes and purified kinases European journal of biochemistry Medium 8841404
1998 Lyn is required for G-CSF-induced DNA synthesis; lyn-deficient chicken B cells transfected with human G-CSFR fail to proliferate in response to G-CSF despite normal JAK1/JAK2 phosphorylation; ectopic Lyn (but not c-Src) restores mitogenic response; kinase-dead Lyn acts as dominant negative. Genetic loss-of-function (lyn-deficient cell lines), rescue with ectopic Lyn or kinase-dead mutant, thymidine incorporation assay The Journal of biological chemistry High 9452436
1998 Lyn negatively regulates BCR signaling by phosphorylating the inhibitory co-receptors FcγRIIB and CD22; in lyn-/- B cells, tyrosine phosphorylation of these co-receptors is severely impaired upon BCR co-ligation, preventing recruitment of SHP-1 and SHIP, and resulting in failure to suppress Ca2+ influx and proliferation. Lyn-/- mouse B cells, co-immunoprecipitation, phosphotyrosine blotting, Ca2+ mobilization assay The Journal of experimental medicine High 9547345
1998 Lyn directly phosphorylates STAT3 in vitro; BCR engagement activates STAT3 in a Lyn-dependent, JAK-independent manner, as shown by failure of JAK1/JAK2 antisense or the JAK inhibitor AG490 to block STAT phosphorylation. In vitro phosphorylation assay, lyn-null cell lines, antisense JAK knockdown, kinase inhibitor, EMSA Oncogene Medium 17146444
1998 Lyn's SH3 domain interacts directly with DNA-PKcs near a leucine zipper homology domain; Lyn phosphorylates DNA-PKcs but not Ku in vitro; this interaction inhibits DNA-PKcs activity and its ability to form a complex with Ku/DNA. Co-immunoprecipitation, GST pulldown with SH3 domain, in vitro kinase assay, DNA-PK activity assay The Journal of biological chemistry Medium 9748231
1999 AMPA receptors physically associate with Lyn in the cerebellum; AMPA receptor stimulation rapidly activates Lyn independently of Ca2+ or Na2+ influx; activated Lyn then activates the MAPK pathway, leading to increased BDNF mRNA expression in a Lyn kinase-dependent manner. Co-immunoprecipitation, in vitro kinase assay, dominant-negative Lyn, BDNF mRNA measurement Nature High 9892356
2000 Lyn functions downstream of the G-CSF receptor; in lyn-deficient cells, G-CSF fails to induce tyrosine phosphorylation of Shc or activation of Erk1/2 or PI3-kinase/Cbl; these pathways are required for DNA synthesis; Ras activation by G-CSF is Lyn-independent. Lyn-deficient DT40 cell lines, phosphotyrosine blotting, kinase assays, dominant-negative constructs Oncogene Medium 10644984
2001 Lyn's SH3 domain interacts with GADD34 (and murine MyD116) identified by yeast two-hybrid and confirmed by GST-SH3 pulldown and co-immunoprecipitation; Lyn phosphorylates GADD34 in vitro and in vivo; wild-type but not kinase-inactive Lyn suppresses GADD34-promoted apoptosis following DNA damage. Yeast two-hybrid, GST-SH3 pulldown, co-immunoprecipitation, in vitro kinase assay, apoptosis assay with kinase-dead mutant Proceedings of the National Academy of Sciences of the USA High 11517336
2001 In J2E erythroleukemic cells, Lyn co-immunoprecipitates with SHP-1, SHP-2, Ras-GAP, STAT5a, STAT5b, and MAPK; dominant-negative Lyn (Y397F) disrupts most of these interactions except with SHP-1; Y397F Lyn blocks erythropoietin-induced differentiation, proliferation, and reduces GATA-1 and EKLF transcription factor levels; Lyn activation requires JAK2. Co-immunoprecipitation, dominant-negative mutant expression, cell differentiation assay, western blot Cancer research Medium 11289114
2002 Lyn kinase associates with the IL-5 receptor alpha (IL-5Rα) under basal conditions in eosinophils and phosphorylates both IL-5Rα and the common beta chain (βcR) in vitro; Lyn is required for IL-5-stimulated eosinophil differentiation. Co-immunoprecipitation, in vitro kinase assay, antisense oligodeoxynucleotide knockdown, Lyn-/- mouse bone marrow differentiation assay Journal of immunology Medium 11823534
2002 DNA-damaging agents Ara-C and daunorubicin activate Lyn and trigger its translocation into sphingomyelin-enriched membrane rafts; raft-compartmentalized Lyn activates neutral sphingomyelinase, generating ceramide; both Lyn translocation and sphingomyelinase activation are blocked by tyrosine kinase inhibitors or raft disruption. Membrane fractionation, immunoblotting, kinase assay, lipid raft disruption, inhibitor studies FASEB journal Medium 12206990
2004 Constitutively active Lyn (Y508F mutant), but not kinase-dead Lyn (K275D), upregulates Bcl-2 mRNA and protein expression in CML cells and protects cells from imatinib-induced apoptosis; Src kinase inhibitor PP2 reduces Lyn activation and Bcl-2 levels in resistant cells. Stable transfection of constitutively active and kinase-dead Lyn mutants, western blot, siRNA, antisense, apoptosis assay The Journal of biological chemistry High 15175350
2004 SHIP1 phosphorylation and PtdIns(3,4,5)P3 metabolism are regulated through Lyn kinase in platelets; Lyn-deficient platelets show enhanced Ca2+ flux and spreading; Lyn and SHIP1 negatively regulate integrin αIIbβ3 outside-in signaling. Lyn-/- and SHIP1-/- mouse platelets, lipid measurement, Ca2+ flux, platelet spreading assay under flow The Journal of biological chemistry Medium 15166241
2004 In lyn-/- mast cells, SHIP tyrosine phosphorylation and activity are markedly reduced, while Fyn kinase shows increased basal and stimulated phosphorylation; these changes result in prolonged FcεRI signaling with elevated PIP3 and excessive degranulation. Lyn-/- bone marrow-derived mast cells, phosphotyrosine blotting, SHIP activity assay, kinase assay, Ca2+ measurement, PIP3 measurement Journal of immunology Medium 15210764
2005 Lyn positively regulates FcεRI signaling and mast cell degranulation at low stimulation intensity via enhanced association with FcεRI beta subunit and activation of Akt and p38, whereas at high stimulation intensity Lyn negatively regulates signaling through the FcεRI beta-ITAM and promotes SHIP and SHP-1 association with FcεRI beta. Wild-type and Lyn-/- mast cells, FcεRI beta ITAM mutants, kinase/phosphatase association assays, degranulation assay Journal of immunology Medium 16272347
2005 In glioblastoma cells, Lyn (but not Fyn) kinase activity promotes cell migration in response to PDGFR-beta and integrin αvβ3 cooperative signaling; Lyn accounts for >90% of pan-Src kinase activity in glioblastoma tumor samples. Migration assay, selective kinase activity measurements, immunoprecipitation kinase assay from tumor biopsies Cancer research Medium 15994925
2005 G-CSF stimulation activates Lyn and Akt in a Lyn-PI3-kinase dependent manner; inhibition of Lyn, PI3-kinase, or Akt abrogates G-CSF-induced reactive oxygen species (ROS) production; G-CSF induces serine phosphorylation and membrane translocation of p47phox (NADPH oxidase subunit) in a Lyn-dependent manner; Lyn-/- neutrophils produce less ROS than wild-type. Lyn-/- mouse neutrophils, pharmacological inhibitors, ROS measurement, p47phox phosphorylation and fractionation Blood Medium 16282349
2006 Lyn is required for P. aeruginosa internalization into lung cells; Lyn activation and its interaction with lipid rafts and TLR2 are required for initial bacterial-host cell interaction; blockade of Lyn prevents bacterial internalization and downstream cytokine induction and apoptosis. Pharmacological inhibition (PP2), dominant-negative mutant, Lyn-/- bone marrow-derived mast cells, internalization assay European journal of immunology Medium 16791881
2006 Lyn phosphorylates Cbp (CSK-binding protein) on tyrosine residues including Tyr314; phospho-Tyr314 recruits Csk/Ctk to suppress Lyn kinase activity (rapid phase) and also recruits SOCS1, leading to ubiquitination and degradation of Lyn (delayed phase) in erythropoietin-stimulated cells. Co-immunoprecipitation, phosphorylation site mapping, Csk/SOCS1 recruitment assay, ubiquitination assay in primary erythroid cells and cell lines The Journal of biological chemistry High 16920712
2006 The C-lobe of the Lyn kinase domain associates with ACSL3 on the Golgi in a conformation-dependent (open conformation required) but kinase activity-independent manner; this interaction is required for Golgi export of Lyn to the plasma membrane; CSK-induced closed conformation prevents ACSL3 association and Golgi export. Co-immunoprecipitation, ACSL3 overexpression/knockdown, live cell imaging, fractionation, domain mutants Journal of cell science High 20605918
2008 Lyn is required for P2X4 receptor upregulation in spinal microglia after nerve injury; Lyn-/- mice show impaired fibronectin-induced P2X4R expression in microglia and reduced tactile allodynia; Lyn is the predominant Src family kinase in spinal microglia. Lyn-/- mice, immunofluorescence, western blot, behavioral assays, primary microglial culture Glia Medium 17918263
2008 Lyn nuclear localization is regulated by Crm1-mediated nuclear export and is enhanced by inhibition of Lyn kinase activity (via SU6656, Csk overexpression, or ATP-binding site mutation); lipid modification (myristoylation/palmitoylation) also limits nuclear accumulation. Leptomycin B treatment, Csk overexpression, kinase-dead mutants, immunofluorescence, nuclear fractionation in HeLa and THP-1 cells Experimental cell research Medium 18817770
2008 Lyn associates with αvβ3 integrin (but not αvβ5) in oligodendrocytes and brain tissue; Lyn suppresses acid sphingomyelinase (ASMase) activity; Lyn knockdown induces apoptosis with ceramide accumulation via ASMase activation; brain ischemia/reperfusion disrupts the αvβ3-Lyn complex and activates ASMase. Co-immunoprecipitation, siRNA knockdown, ASMase activity assay, ceramide measurement, brain fractionation The Journal of biological chemistry Medium 18682390
2009 Lyn forms a complex with RANK, SHP-1, and Gab2 in osteoclast precursors; upon RANKL stimulation in Lyn-/- cells, Gab2 phosphorylation and JNK and NF-κB activation are enhanced; Lyn negatively regulates osteoclast differentiation (not activity) downstream of RANK. Co-immunoprecipitation, Lyn-/- mouse osteoclast cultures, kinase/phosphorylation assays, in vivo bone resorption assay Proceedings of the National Academy of Sciences of the USA Medium 19171907
2010 Lyn phosphorylates SHP-1 at Tyr564 (required for maximal phosphatase activity) and Tyr536 (required for efficient STAT5 interaction); in lyn-/-;PLC-β3-/- hematopoietic stem cells, both phosphorylation events are abrogated, resulting in reduced SHP-1 activity and constitutive STAT5 activation causing CMML-like disease. In vitro kinase assay with phosphosite mutants, phospho-specific antibodies, mouse genetics (double KO), STAT5 activation assays Blood High 20858858
2010 RNAi-mediated knockdown of LYN in mesenchymal breast cancer lines inhibits cell migration and invasion but not proliferation; dasatinib at nanomolar concentrations blocks invasion consistent with LYN kinase inhibition. RNAi knockdown, cell migration and invasion assay, pharmacological inhibition Cancer research Medium 20215510
2011 Lyn is required for PECAM-1 tyrosine phosphorylation and subsequent recruitment of SHP-2 to PECAM-1 in platelets; PECAM-1-deficient and Lyn-deficient platelets show equal hyperresponsiveness to GPVI stimulation, establishing that they function in the same inhibitory pathway. PECAM-1-/- and Lyn-/- mouse platelets, PECAM-1/Lyn double-deficient mice, co-immunoprecipitation, platelet activation assays Blood High 21297004
2012 Yes and Lyn interact with EGFR in cetuximab-resistant cells (but not sensitive cells); knockdown of either Yes or Lyn abolishes EGFR nuclear translocation; Lyn/Yes phosphorylate EGFR at Y1101, which is required for nuclear entry; nuclear EGFR complexes bind B-Myb and iNOS promoters. Co-immunoprecipitation, RNAi knockdown, overexpression, ChIP assay, site-directed mutagenesis (Y1101) Oncogene Medium 22430206
2013 Lyn associates with FAK and phosphorylates FAK at tyrosines 576/577 and 925; this Lyn-FAK interaction is required for Lyn-dependent stabilization of endothelial adherens junctions; Lyn-/- mice show increased vascular permeability in response to LPS or VEGF. Co-immunoprecipitation, constitutively active Lyn, siRNA knockdown, Lyn-/- mice, permeability assays Blood High 24108461
2013 Lyn phosphorylates the atypical kinase SgK269/PEAK1 at Y635, which is a Grb2-binding site promoting Stat3 and Erk activation; SgK269 Y635F mutant fails to enhance acinar size or cellular invasion, placing Lyn upstream of SgK269 in a basal breast cancer signaling pathway. In vitro kinase substrate identification, phosphosite mutant (Y635F), 3D culture, invasion assays, Stat3/Erk activation measurement Cancer research Medium 23378338
2016 Lyn physically interacts with IRF5 and inhibits IRF5 ubiquitination and phosphorylation in the TLR-MyD88 pathway, thereby suppressing IRF5 transcriptional activity in a kinase activity-independent manner; monoallelic Irf5 deletion alleviates cytokine hyperproduction in Lyn-/- dendritic cells and SLE-like disease in Lyn-/- mice. Co-immunoprecipitation, ubiquitination assay, Lyn kinase-inactive mutant, Lyn-/-Irf5+/- double mutant mice, cytokine measurement Immunity High 27521268
2017 Lyn phosphorylates SHP-1 at tyrosine 536, activating the phosphatase and promoting inhibitory immunoreceptor signaling; by contrast, Fyn phosphorylates SHP-1 at serine 591, inactivating it and enabling activatory signaling; these opposing modifications on SHP-1 determine whether immunoreceptor signaling results in homeostasis or inflammation. In vitro kinase assays, phospho-specific antibodies, Lyn-/- and Fyn-/- mice, SHP-1 phosphomutants Nature communications High 28811476
2017 Lyn kinase controls SNAI family protein localization and stability through the Vav-Rac1-PAK1 signaling pathway; targeting Lyn in vitro reduces EMT markers and in vivo reduces metastasis of primary tumors. Lyn knockdown/inhibition, pathway inhibitors, in vivo tumor metastasis assay, EMT marker analysis Oncogene Medium 28288135
2017 LPS-induced Lyn palmitoylation, SH2- and SH3-mediated interactions, and catalytic activity are all required for Lyn accumulation in membrane rafts; raft-associated Lyn negatively regulates TLR4-induced TNF-α, CCL5/RANTES production, and NF-κB/IRF3 activity in macrophages. Lyn-GFP domain mutants overexpressed in RAW264 macrophages and peritoneal macrophages, membrane fractionation, cytokine measurement, NF-κB/IRF3 reporter assays, Lyn siRNA silencing Molecular biology of the cell Medium 28228554
2018 LYN activity is modulated by the prolyl isomerase PIN1 in BRCA1-mutant triple-negative breast cancer; the full-length LYN splice isoform (but not the Δaa25-45 variant) drives migration and invasion of aggressive TNBC cells; LYN is a downstream effector of c-KIT in normal mammary cells. Isoform-specific expression, RNAi knockdown, migration and invasion assays, PIN1 manipulation Cell reports Medium 30590041
2019 CARD9 is a vital component of Lyn-mediated regulation of TLR2 and TLR4 signaling in dendritic cells; in the absence of Lyn, a CD11b-Syk-PKCδ-CARD9 pathway is amplified, leading to increased TLR-induced inflammatory cytokines; dendritic cell-specific CARD9 deletion reverses autoimmunity in Lyn-deficient mice. Lyn-/-CARD9-/- double KO mice, dendritic cell-specific CARD9 deletion, cytokine assays, pathway inhibitor studies Science signaling Medium 31594855
2020 High ECM stiffness induces ligand-independent phosphorylation of EPHA2, which recruits and activates LYN kinase; LYN phosphorylates TWIST1, releasing it from its cytoplasmic anchor G3BP2 to enter the nucleus and trigger EMT and invasion; genetic and pharmacological inhibition prevents breast tumor metastasis in vivo. Co-immunoprecipitation, phosphorylation assays, siRNA/genetic KO, in vivo tumor metastasis models, mechanically tunable substrates Developmental cell High 32574556
2020 Lyn kinase is critical for flavivirus (Dengue, Zika) secretion within autophagosome-derived vesicles; kinase-deficient and palmitoylation-deficient Lyn mutants fail to rescue virus release in Lyn-/- cells; Lyn-dependent viral egress requires Ulk1, Rab GTPases, and SNARE complexes implicated in secretory autophagy. Lyn-/- cells, reconstitution with WT or mutant Lyn, pharmacological inhibition, viral titer, autophagosome imaging Nature communications High 33060596
2021 CBL mutations increase LYN activation and interaction with mutant CBL, driving enhanced CBL phosphorylation, PIK3R1 (p85α) recruitment, and downstream PI3K/AKT signaling; genetic ablation or dasatinib-mediated inhibition of LYN reduces CBL phosphorylation and CBL-PIK3R1 interaction. Mass spectrometry phosphoproteomics, co-immunoprecipitation, genetic LYN ablation, dasatinib treatment, functional assays in CBL-mutant cell lines and primary CMML Blood High 33512474
2022 Fumarate directly succinates LYN at cysteine C381, covalently inhibiting LYN kinase activity; this blocks BCR signaling and B-cell activation, proliferation, and antibody production in vitro and in vivo; FH inhibition or dimethyl-fumarate treatment suppresses B-cell activation through this LYN-dependent mechanism. In vitro kinase assay, mass spectrometry for succination site (C381), fumarate hydratase inhibition, dimethyl-fumarate treatment, B-cell functional assays in vitro and in vivo Nature chemical biology High 35710616
2023 Constitutively activating LYN mutations (p.Y508*, p.Q507*, p.Y508F) in humans increase ICAM-1 expression on endothelial cells and β2-integrin expression on neutrophils, enhancing neutrophil adhesion and transendothelial migration, causing cutaneous vasculitis and liver fibrosis; dasatinib (Lyn inhibitor) resolved liver fibrosis in a patient. Next-generation sequencing, patient-derived endothelial cells (iECs), neutrophil adhesion/TEM assays, dasatinib treatment in patients Nature communications Medium 36932076

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways. The EMBO journal 617 8137818
2003 BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 553 12509383
1991 Association of B cell antigen receptor with protein tyrosine kinase Lyn. Science (New York, N.Y.) 479 1702903
2005 Lyn tyrosine kinase: accentuating the positive and the negative. Immunity 286 15664155
1999 The AMPA receptor interacts with and signals through the protein tyrosine kinase Lyn. Nature 240 9892356
2020 Matrix Rigidity Controls Epithelial-Mesenchymal Plasticity and Tumor Metastasis via a Mechanoresponsive EPHA2/LYN Complex. Developmental cell 213 32574556
2004 A Bcr/Abl-independent, Lyn-dependent form of imatinib mesylate (STI-571) resistance is associated with altered expression of Bcl-2. The Journal of biological chemistry 208 15175350
1995 G protein-coupled chemoattractant receptors regulate Lyn tyrosine kinase.Shc adapter protein signaling complexes. The Journal of biological chemistry 158 7650013
1998 A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals. The Journal of experimental medicine 149 9547345
2012 Functions of the Lyn tyrosine kinase in health and disease. Cell communication and signaling : CCS 146 22805580
2000 Redundant and opposing functions of two tyrosine kinases, Btk and Lyn, in mast cell activation. Journal of immunology (Baltimore, Md. : 1950) 137 10903718
2010 LYN is a mediator of epithelial-mesenchymal transition and a target of dasatinib in breast cancer. Cancer research 128 20215510
2008 Association between imatinib-resistant BCR-ABL mutation-negative leukemia and persistent activation of LYN kinase. Journal of the National Cancer Institute 125 18577747
1996 Altered antigen receptor signaling and impaired Fas-mediated apoptosis of B cells in Lyn-deficient mice. The Journal of experimental medicine 124 9064343
2009 Multiple roles of Lyn kinase in myeloid cell signaling and function. Immunological reviews 121 19290919
2005 Positive and negative regulation of mast cell activation by Lyn via the FcepsilonRI. Journal of immunology (Baltimore, Md. : 1950) 121 16272347
2005 G-CSF induced reactive oxygen species involves Lyn-PI3-kinase-Akt and contributes to myeloid cell growth. Blood 119 16282349
2013 B cell-specific loss of Lyn kinase leads to autoimmunity. Journal of immunology (Baltimore, Md. : 1950) 108 24376269
2001 B-cell kinase lyn deficiency in patients with systemic lupus erythematosus. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 105 11288756
2017 Lyn and Fyn function as molecular switches that control immunoreceptors to direct homeostasis or inflammation. Nature communications 98 28811476
2004 Dysregulated FcepsilonRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells. Journal of immunology (Baltimore, Md. : 1950) 93 15210764
2005 Lyn kinase activity is the predominant cellular SRC kinase activity in glioblastoma tumor cells. Cancer research 90 15994925
2016 Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity. Immunity 89 27521268
2008 Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. Glia 89 17918263
1998 Requirement of Src kinase Lyn for induction of DNA synthesis by granulocyte colony-stimulating factor. The Journal of biological chemistry 86 9452436
1999 Therapeutic targeting of Src-kinase Lyn in myeloid leukemic cell growth. Leukemia 85 10360372
2009 Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation. Immunity 81 19362019
2013 Involvement of Lyn and the atypical kinase SgK269/PEAK1 in a basal breast cancer signaling pathway. Cancer research 79 23378338
1998 Positive and negative roles of the tyrosine kinase Lyn in B cell function. Seminars in immunology 76 9695186
2016 LYN Kinase in the Tumor Microenvironment Is Essential for the Progression of Chronic Lymphocytic Leukemia. Cancer cell 75 27728807
2012 Yes and Lyn play a role in nuclear translocation of the epidermal growth factor receptor. Oncogene 74 22430206
2004 SHIP1 and Lyn Kinase Negatively Regulate Integrin alpha IIb beta 3 signaling in platelets. The Journal of biological chemistry 73 15166241
2016 Targeting BCL-2 and ABL/LYN in Philadelphia chromosome-positive acute lymphoblastic leukemia. Science translational medicine 71 27582059
2005 Activation of Src kinase Lyn by the Kaposi sarcoma-associated herpesvirus K1 protein: implications for lymphomagenesis. Blood 71 15665117
2011 B cell-derived IL-10 suppresses inflammatory disease in Lyn-deficient mice. Proceedings of the National Academy of Sciences of the United States of America 69 21911371
2009 Developmental acquisition of the Lyn-CD22-SHP-1 inhibitory pathway promotes B cell tolerance. Journal of immunology (Baltimore, Md. : 1950) 67 19380785
2001 Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis. Proceedings of the National Academy of Sciences of the United States of America 66 11517336
2021 The Src-family Kinase Lyn in Immunoreceptor Signaling. Endocrinology 64 34320188
2013 A critical role for Lyn kinase in strengthening endothelial integrity and barrier function. Blood 62 24108461
1998 Role for tyrosine phosphorylation and Lyn tyrosine kinase in fas receptor-mediated apoptosis in eosinophils. Blood 62 9657755
2015 Neuroblastoma tyrosine kinase signaling networks involve FYN and LYN in endosomes and lipid rafts. PLoS computational biology 59 25884760
2004 Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of hematopoietic cell lines and primary megakaryocytic progenitors. Blood 58 14726379
2020 Lyn kinase regulates egress of flaviviruses in autophagosome-derived organelles. Nature communications 57 33060596
1998 Independent and opposing roles for Btk and lyn in B and myeloid signaling pathways. The Journal of experimental medicine 57 9730885
2010 Lyn- and PLC-beta3-dependent regulation of SHP-1 phosphorylation controls Stat5 activity and myelomonocytic leukemia-like disease. Blood 55 20858858
2019 Quercetin as a Lyn kinase inhibitor inhibits IgE-mediated allergic conjunctivitis. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 53 31672514
2016 Lyn Delivers Bacteria to Lysosomes for Eradication through TLR2-Initiated Autophagy Related Phagocytosis. PLoS pathogens 52 26735693
2000 Involvement of Shc and Cbl-PI 3-kinase in Lyn-dependent proliferative signaling pathways for G-CSF. Oncogene 51 10644984
2018 Lyn, Lupus, and (B) Lymphocytes, a Lesson on the Critical Balance of Kinase Signaling in Immunity. Frontiers in immunology 50 29545808
2018 Dual Mechanisms of LYN Kinase Dysregulation Drive Aggressive Behavior in Breast Cancer Cells. Cell reports 49 30590041
2001 Maturation of erythroid cells and erythroleukemia development are affected by the kinase activity of Lyn. Cancer research 48 11289114
2016 Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma. EBioMedicine 47 28024734
2007 MyD88-dependent autoimmune disease in Lyn-deficient mice. European journal of immunology 47 17853409
2006 Src kinase Lyn is crucial for Pseudomonas aeruginosa internalization into lung cells. European journal of immunology 47 16791881
2006 Engagement of the B-cell antigen receptor activates STAT through Lyn in a Jak-independent pathway. Oncogene 46 17146444
2005 The Lyn tyrosine kinase differentially regulates dendritic cell generation and maturation. Journal of immunology (Baltimore, Md. : 1950) 46 16116174
2003 Reduced dosage of Bruton's tyrosine kinase uncouples B cell hyperresponsiveness from autoimmunity in lyn-/- mice. Journal of immunology (Baltimore, Md. : 1950) 46 12902486
2022 Sorafenib inhibits LPS-induced inflammation by regulating Lyn-MAPK-NF-kB/AP-1 pathway and TLR4 expression. Cell death discovery 45 35680841
2017 Lyn regulates mucus secretion and MUC5AC via the STAT6 signaling pathway during allergic airway inflammation. Scientific reports 44 28205598
1995 LPS and Taxol activate Lyn kinase autophosphorylation in Lps(n), but not in Lpsd), macrophages. Molecular medicine (Cambridge, Mass.) 44 8521300
1993 Association of Src-family kinase Lyn with B-cell antigen receptor. Immunological reviews 44 8349296
2010 Bafetinib, a dual Bcr-Abl/Lyn tyrosine kinase inhibitor for the potential treatment of leukemia. Current opinion in investigational drugs (London, England : 2000) 43 21154127
2011 Lyn and PECAM-1 function as interdependent inhibitors of platelet aggregation. Blood 42 21297004
2008 Nuclear localization of Lyn tyrosine kinase mediated by inhibition of its kinase activity. Experimental cell research 42 18817770
2006 Lyn kinase promotes erythroblast expansion and late-stage development. Blood 41 16705093
2006 Csk-binding protein mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells. The Journal of biological chemistry 41 16920712
2018 MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway. Cancer cell international 40 30524205
2010 The Lyn kinase C-lobe mediates Golgi export of Lyn through conformation-dependent ACSL3 association. Journal of cell science 40 20605918
1997 Lyn, a src-like tyrosine kinase. The international journal of biochemistry & cell biology 39 9202419
2009 The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America 38 19171907
2008 Integrin-associated Lyn kinase promotes cell survival by suppressing acid sphingomyelinase activity. The Journal of biological chemistry 38 18682390
2002 Lyn tyrosine kinase is important for IL-5-stimulated eosinophil differentiation. Journal of immunology (Baltimore, Md. : 1950) 38 11823534
2002 Ara-C- and daunorubicin-induced recruitment of Lyn in sphingomyelinase-enriched membrane rafts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 12206990
2006 Increased megakaryocytopoiesis in Lyn-deficient mice. Oncogene 37 16418722
2022 Fumarate suppresses B-cell activation and function through direct inactivation of LYN. Nature chemical biology 36 35710616
2012 Lyn kinase mediates cell motility and tumor growth in EGFRvIII-expressing head and neck cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 34 22490227
2005 Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress erythropoiesis. Oncogene 34 15516974
1998 Regulation of DNA-dependent protein kinase by the Lyn tyrosine kinase. The Journal of biological chemistry 34 9748231
2017 Targeting Lyn regulates Snail family shuttling and inhibits metastasis. Oncogene 33 28288135
2017 Src family kinases Fyn and Lyn are constitutively activated and mediate plasmacytoid dendritic cell responses. Nature communications 33 28368000
1998 Abrogation of autoimmune disease in Lyn-deficient mice by the mutation of the Btk gene. International immunology 33 9620599
2021 CBL mutations drive PI3K/AKT signaling via increased interaction with LYN and PIK3R1. Blood 32 33512474
2015 Astaxanthin Improves Human Sperm Capacitation by Inducing Lyn Displacement and Activation. Marine drugs 32 26308013
2006 Class A scavenger receptor-mediated cell adhesion requires the sequential activation of Lyn and PI3-kinase. American journal of physiology. Cell physiology 32 17192284
2018 Hematopoietic cell-specific lyn substrate (HCLS1 or HS1): A versatile actin-binding protein in leukocytes. Journal of leukocyte biology 31 30537294
2021 Therapeutic targeting of Lyn kinase to treat chorea-acanthocytosis. Acta neuropathologica communications 30 33941276
2014 LYN-activating mutations mediate antiestrogen resistance in estrogen receptor-positive breast cancer. The Journal of clinical investigation 30 25401474
1996 The Lyn-catalyzed Tyr phosphorylation of the transmembrane band-3 protein of human erythrocytes. European journal of biochemistry 30 8841404
2003 The Src kinase Lyn is a negative regulator of mast cell proliferation. Journal of leukocyte biology 28 14525964
2000 Pleiotropic role of lyn kinase in leukotriene B(4)-induced eosinophil activation. Blood 28 10828041
2023 Lyn-mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn. Journal of cellular and molecular medicine 27 37132040
2019 CARD9 mediates dendritic cell-induced development of Lyn deficiency-associated autoimmune and inflammatory diseases. Science signaling 27 31594855
2015 Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin αIIbβ3 and Lyn Kinase. PloS one 26 26291522
2014 Lyn tyrosine kinase regulates androgen receptor expression and activity in castrate-resistant prostate cancer. Oncogenesis 26 25133482
2012 Lyn but not Fyn kinase controls IgG-mediated systemic anaphylaxis. Journal of immunology (Baltimore, Md. : 1950) 26 22450804
2017 Association of Lyn kinase with membrane rafts determines its negative influence on LPS-induced signaling. Molecular biology of the cell 25 28228554
2006 The association between CD36 and Lyn protein tyrosine kinase is mediated by lipid. Biochemical and biophysical research communications 24 17052693
2023 Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome. Nature communications 23 36932076
1999 Distinctive roles of Fyn and Lyn in IgD- and IgM-mediated signaling. International immunology 23 10464165
2011 Elevated BCR signaling and decreased survival of Lyn-deficient transitional and follicular B cells. European journal of immunology 22 21928281

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