Affinage

ICAM4

Intercellular adhesion molecule 4 · UniProt Q14773

Length
271 aa
Mass
29.3 kDa
Annotated
2026-06-10
74 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ICAM4 (LW blood group glycoprotein/CD242) is an erythroid-specific, single-pass transmembrane intercellular adhesion molecule of the immunoglobulin superfamily that functions as a promiscuous integrin ligand controlling red-cell adhesive interactions in erythropoiesis, red-cell clearance, and vaso-occlusion (PMID:8202485, PMID:8566017, PMID:16690966). Originally defined as a heavily N-glycosylated 37–47 kDa erythrocyte surface glycoprotein associated with the cytoskeleton and physically clustered with the Rh protein, its cloning revealed two extracellular Ig-like domains (~30% identity to ICAM-1/-2/-3) and formally placed it in the ICAM family (PMID:2424433, PMID:2514351, PMID:8202485). Through these D1 and D2 domains ICAM4 engages a broad panel of integrins—the leukocyte β2 integrins LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18) and CD11c/CD18, the platelet integrin αIIbβ3, and αV-family integrins including αVβ3—at partially overlapping but mechanistically distinct contact sites mapped by systematic mutagenesis and domain deletion, in a divalent-cation-dependent manner (PMID:8566017, PMID:10846180, PMID:12477717, PMID:14551135, PMID:15355350, PMID:16985175). ICAM-4/αV adhesion mediates attachment of erythroblasts to bone-marrow macrophages and is required for erythroblastic island formation, as ICAM-4 knockout mice and peptide-blocking experiments show markedly reduced island numbers (PMID:16690966); ICAM-4/CD11c interactions contribute to macrophage erythrophagocytosis of senescent red cells (PMID:16985175). On sickle erythrocytes, epinephrine acting through β-adrenergic receptors activates a cAMP–PKA/AKAP-dependent pathway that phosphorylates ICAM-4 on serine and, via Gαs-driven p60-c-Src, on tyrosine, increasing the frequency and strength of ICAM-4 binding to endothelial αVβ3 and promoting vaso-occlusion in vivo, an effect blocked by propranolol, soluble recombinant LW, or AT1R blockade (PMID:15308566, PMID:16738001, PMID:17609430, PMID:26007235, PMID:28076805, PMID:31083675).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 1990 High

    Establishing that the LW antigen resides on a discrete, externally-oriented, glycosylation-dependent erythrocyte glycoprotein distinct from Rh set the structural groundwork for treating LW as a defined membrane protein rather than a modified Rh species.

    Evidence Immunoblotting, enzymatic surface topology mapping (carboxypeptidase Y), glycanase digestion, and comparative iodopeptide mapping against RhD on human erythrocytes

    PMID:1979326 PMID:2112034 PMID:2424433 PMID:2514351

    Open questions at the time
    • Molecular identity and primary sequence not yet determined
    • Functional ligand activity unknown at this stage
    • Nature of the Rh-LW association left biochemically undefined
  2. 1994 High

    Cloning the LW cDNA answered what the protein is, revealing a two-Ig-domain single-pass transmembrane ICAM-family member with a secreted isoform, reclassifying LW as ICAM-4.

    Evidence cDNA library screening and PCR cloning from human bone marrow with antibody-based protein validation

    PMID:8202485

    Open questions at the time
    • Integrin ligand specificity not yet tested
    • Physiological role of the secreted isoform undefined
    • Tissue-restricted expression mechanism not established
  3. 1996 High

    Defining the gene's three-exon architecture, GATA-1-containing erythroid promoter, and a loss-of-function deletion in an LW(a-b-) individual established the genetic basis of erythroid-specific expression and the LW-null phenotype.

    Evidence Genomic sequencing, K562 promoter-reporter transfection, and mutation analysis of an LW-negative donor

    PMID:8639917

    Open questions at the time
    • Phenotypic consequences of complete LW deficiency in the donor not detailed
    • Regulation of the secreted versus membrane isoform splicing unaddressed
  4. 2003 High

    Systematic mutagenesis of the integrin-binding surfaces answered how a single small Ig molecule engages multiple integrins, mapping distinct but adjacent contact footprints for β2, αIIbβ3, αVβ3, and αV integrins across D1 and D2.

    Evidence Recombinant ICAM-4-Fc, domain deletions, point mutagenesis, integrin transfectants, patient/deficient cells, and synthetic peptide inhibition

    PMID:10846180 PMID:12477717 PMID:14551135 PMID:15355350 PMID:8566017

    Open questions at the time
    • No co-crystal structure of any ICAM-4/integrin complex
    • Affinity hierarchy across integrins not quantified
    • Glycosylation effects on binding only partially resolved
  5. 2006 High

    Knockout and reconstitution experiments established ICAM-4/αV adhesion as physiologically required for erythroblastic island formation, and ICAM-4/CD11c as contributing to senescent red-cell clearance, defining the molecule's roles in erythropoiesis and red-cell turnover.

    Evidence ICAM-4 knockout mice, in vitro island reconstitution with peptide blockade, αV expression analysis on island macrophages, and erythrophagocytosis inhibition assays

    PMID:10895261 PMID:16690966 PMID:16985175

    Open questions at the time
    • Residual island formation in null marrow implies redundant adhesion systems not identified
    • Quantitative contribution of ICAM-4 to in vivo red-cell lifespan not measured
  6. 2007 High

    Demonstrating epinephrine-driven, PKA-dependent ICAM-4 serine phosphorylation that activates sickle-RBC adhesion to endothelial αVβ3 and causes vaso-occlusion connected adrenergic signaling to a defined adhesive pathology.

    Evidence Adhesion assays with cAMP/PKA pharmacology, LW immunoprecipitation/phosphorylation detection, and in vivo nude-mouse vaso-occlusion with propranolol and soluble-LW blockade

    PMID:15308566 PMID:16738001 PMID:17609430

    Open questions at the time
    • Direct PKA phosphorylation sites on ICAM-4 not mapped
    • Mechanism linking phosphorylation to increased integrin binding not defined
  7. 2021 Medium

    Single-molecule and pharmacological dissection refined the upstream regulation, implicating Gαs/c-Src-dependent tyrosine phosphorylation, AKAP-anchored cAMP-PKA control of active-receptor density, and renin-angiotensin (AT1R) cross-talk in tuning ICAM-4 activity.

    Evidence AFM force spectroscopy across RBC genotypes with cholera/pertussis toxins, forskolin, AKAP inhibitors, valsartan, and co-immunoprecipitation of LW with p60-c-Src

    PMID:22404936 PMID:26007235 PMID:28076805 PMID:31083675

    Open questions at the time
    • c-Src/LW interaction rests on single-lab co-IP without reciprocal validation
    • AKAP isoform and direct ICAM-4 anchoring partner unidentified
    • Mechanistic basis of AT1R/β-AR convergence on ICAM-4 unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How conformational or phosphorylation-driven changes in ICAM-4 translate into selective activation of distinct integrin partners, and the structural basis of multi-integrin recognition, remain unresolved.
  • No atomic-resolution structure of ICAM-4 or its integrin complexes
  • Link between cytoplasmic-tail phosphorylation and ectodomain integrin binding not mechanistically defined
  • Physiological function of the secreted ICAM-4S isoform unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 7 GO:0005198 structural molecule activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2
Partners
ITGA2BITGALITGAMITGAVITGAXITGB2ITGB3SRC
Complex memberships
Rh complex (Rh-LW membrane cluster)erythroblastic island

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 The LW blood group antigen (ICAM4) is carried on a glycoprotein of Mr 37,000–47,000 on human erythrocytes. N-glycosidically linked oligosaccharides are required for LW antigen epitope formation (destroyed by endoglycosidase F treatment). The LW polypeptide is associated with the erythrocyte cytoskeleton. Immunoblotting with monoclonal antibodies, endoglycosidase F treatment, radioiodinated antibody quantitation, cytoskeleton fractionation The Biochemical journal High 2424433
1989 The LW glycoprotein carries approximately 8–9 N-linked and only 1–2 O-linked oligosaccharide chains, as shown by N-glycanase and O-glycanase digestion. A minor 31 kDa component co-immunoprecipitated with LW was identified as the Rh protein, suggesting Rh and LW antigens are associated in the membrane as a functional complex (Rh cluster). Immunoprecipitation, SDS-PAGE, N-glycanase and O-glycanase digestion, two-dimensional peptide mapping Molecular immunology Medium 2514351
1990 The C-terminal domain of the LW polypeptide is exposed at the external surface of human erythrocytes, as demonstrated by carboxypeptidase Y digestion destroying surface 125I label and LW antigens but not affecting intracellular-facing domains. LW antigen expression requires Mg2+ (selectively restored by Mg2+ but not Mn2+ or Ca2+ after EDTA treatment). N- and O-glycanase removal of sugar chains does not significantly alter LW epitopes recognized by monoclonal antibody. Carboxypeptidase Y and aminopeptidase M digestion of intact erythrocytes and vesicles, radioiodination, EDTA treatment and divalent cation restoration, glycanase digestion The Journal of biological chemistry High 1979326
1990 The RhD polypeptide and LW glycoprotein are distinct proteins that share some common protein domains (5 of >20 iodopeptides co-migrate), but LW carries N-linked carbohydrates (N-glycanase alters LW map) while Rh does not. LW is neither a glycosylated form of Rh protein nor a precursor. Two-dimensional iodopeptide mapping after chymotrypsin digestion, 125I-labeling (chloramine-T and Bolton-Hunter), N-glycanase treatment Blood High 2112034
1994 The LW blood group glycoprotein was cloned from a human bone marrow cDNA library and found to encode a 270-amino acid single-pass transmembrane protein (and a secreted 236-residue isoform). The protein shows ~30% sequence identity with ICAM-1, -2, and -3, with two Ig-like extracellular domains and a conserved LFA-1 binding region, formally classifying LW as a member of the ICAM family. cDNA library screening, PCR cloning, sequence analysis, immunoblotting with anti-N-terminal peptide antibody, indirect agglutination Proceedings of the National Academy of Sciences of the United States of America High 8202485
1995 The LW (ICAM-4) red cell glycoprotein binds to leukocyte-specific integrins CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1), and CD11c/CD18, identifying it as a functional intercellular adhesion molecule on red blood cells. Cell adhesion assays, integrin binding assays European journal of immunology Medium 8566017
1996 The LW gene is organized into three exons spanning ~2.65 kb. The exon/intron architecture correlates with structural protein domains. The 5'UTR contains GATA-1 and other erythroid transcription factor binding sites and drives transcription in erythroleukemic K562 cells. A 10-bp deletion in exon 1 generating a premature stop codon was identified in one LW(a-b-) individual, producing a truncated protein without transmembrane/cytoplasmic domains. Genomic DNA sequencing, PCR amplification, transfection of 5'UTR into K562 cells for transcriptional activity Blood High 8639917
1999 LW glycoprotein (ICAM-4) binds VLA-4 (alpha4beta1) and alphaV-containing integrins. During erythropoiesis, LW expression precedes Lutheran glycoprotein expression, and LW on erythroblasts may interact with VLA-4 on macrophages to stabilize erythroblastic islands in bone marrow. In vitro erythropoiesis cultures, adhesion assays, expression timing studies Bailliere's best practice & research. Clinical haematology Medium 10895261
2000 LFA-1 (CD11a/CD18) binds to the first Ig-like domain (D1) of ICAM-4 via residues Leu80, Trp93, Arg97 on the CFG face and Trp77 on the E-F loop. Mac-1 (CD11b/CD18) binding site encompasses both D1 and D2, with key residues on the CFG face of D1 and Glu151/Thr154 in the C'-E loop of D2. The R52E and T91Q mutations (corresponding to key ICAM-1/LFA-1 contact residues) had no effect on ICAM-4/LFA-1 binding, indicating a distinct binding mode. Binding requires divalent cations Ca2+ and Mg2+. Recombinant ICAM-4-Fc protein generation, domain deletion mutants, site-directed mutagenesis of 22 residues, cellular adhesion assays with LFA-1 and Mac-1 L-cell transfectants, molecular modeling based on ICAM-2 crystal structure The Journal of biological chemistry High 10846180
2002 ICAM-4 (LW) is a novel ligand for platelet-activated alphaIIbbeta3 integrin (GPIIb-IIIa). Activated platelets adhere to ICAM-4-positive but not ICAM-4-negative RBCs; inhibition by anti-beta3 and anti-alphaIIbbeta3 antibodies but not anti-GPIb, CD36, or CD47. Platelets from Glanzmann thrombasthenia patients (lacking alphaIIbbeta3) do not bind ICAM-4. The binding site encompasses ICAM-4 Ig domains D1 and D2, with the G65-V74 sequence of D1 playing a role. Cell adhesion assays with RBCs, platelets, ICAM-4-Fc fusion proteins; inhibition with monoclonal antibodies; CHO transfectants expressing alphaIIbbeta3; domain deletion analysis; synthetic peptide inhibition; patient cells (Glanzmann thrombasthenia) The Journal of biological chemistry High 12477717
2002 A novel secreted isoform of ICAM-4 (ICAM-4S), encoded by an alternatively spliced cDNA lacking the membrane-spanning domain, is expressed in erythroblasts. COS-7 cells transfected with GFP-ICAM-4S show different subcellular localization than the membrane form, and ICAM-4S protein is secreted into culture medium. ICAM-4S may modulate membrane-associated ICAM-4 interactions. cDNA cloning, GFP fusion constructs transfected into COS-7 cells, live imaging, conditioned medium analysis, murine ICAM-4 cloning and recombinant protein adhesion assays Blood Medium 12406883
2003 Systematic mutagenesis of surface-exposed residues conserved between human and murine ICAM-4 identified 12 single amino-acid changes affecting interaction with alphaV integrins. Ten mutations reduced adhesion (8 spatially clustered), and 2 mutations increased adhesion by apparently preventing N160 glycosylation. The alphaV integrin binding site is adjacent to but distinct from the alphaLbeta2 and alphaMbeta2 binding sites. Site-directed mutagenesis, cell adhesion assays with alphaV integrin-expressing cells, synthetic peptide inhibition Blood High 14551135
2004 Epinephrine activates sickle (but not normal) erythrocyte adhesion to endothelial cells via a cAMP-PKA-dependent pathway. PKA-dependent serine phosphorylation of ICAM-4 (LW) was demonstrated by immunoprecipitation of LW from sickle erythrocytes treated with epinephrine. The major counter-receptor for LW on endothelial cells was identified as alphaVbeta3 integrin. Cell adhesion assays, cAMP/PKA inhibitor/activator pharmacology, immunoprecipitation of LW followed by detection of serine phosphorylation, serine/threonine phosphatase inhibitor experiments Blood High 15308566
2004 alphaLbeta2, alphaMbeta2, and activated alphaIIbbeta3 bind specifically to ICAM-4-Fc. ICAM-4 failed to interact with alpha4beta1 even after activation. The beta3 integrin (alphaIIbbeta3 and alphaVbeta3) binding sites encompass both D1 and D2 Ig domains, but alphaIIbbeta3 contacts the ABED face of D1 with extension to the C'-E loop of D2, while alphaVbeta3 contacts residues on both faces of D1 and the C'-E loop of D2. Cell transfectants expressing individual integrins, ICAM-4-Fc adhesion assays, domain deletion analysis, site-directed mutagenesis, synthetic peptide inhibition, beta2-integrin-deficient LAD cells European journal of biochemistry High 15355350
2006 ICAM-4 is critical for erythroblastic island formation in vivo and in vitro. ICAM-4 knockout mice show a striking decrease in erythroblastic islands in vivo. In vitro island reconstitution from ICAM-4 null marrow shows a 47% decrease compared to wild-type. Peptides blocking ICAM-4/alphaV adhesion reduce reconstituted islands by 53–57%. AlphaV integrin is expressed on macrophages isolated from erythroblastic islands, confirming ICAM-4/alphaV as the functional adhesion pair. ICAM-4 knockout mouse generation, quantitative live-cell island harvesting and in vitro reconstitution assay, peptide blocking experiments, alphaV integrin expression on isolated island macrophages Blood High 16690966
2006 ICAM-4 on sickle RBCs binds endothelial alphaVbeta3 to mediate adhesion and vaso-occlusion. Synthetic peptides based on alphaV-binding domains of ICAM-4 (FWV and ATSR) markedly decreased sickle RBC adhesion and prevented vessel blockage in an ex vivo rat mesocecum microvascular model. Fluoresceinated ATSR co-localized with vascular endothelium, and this was blocked by anti-alphaVbeta3 antibody. Ex vivo rat mesocecum microvascular model with intravital microscopy, synthetic peptide infusion, fluorescent peptide localization, anti-alphaVbeta3 blocking antibody American journal of physiology. Cell physiology High 16738001
2006 ICAM-4 functions as a ligand for monocyte/macrophage-specific CD11c/CD18 integrin. Both Ig domains of ICAM-4 contain binding sites for CD11c/CD18, with key residues clustering in two regions of domain D1 with extension to D2. Inhibition of erythrophagocytosis by anti-ICAM-4 and anti-integrin antibodies suggests a role for ICAM-4/CD11c interactions in removal of senescent red cells. Cell adhesion assays, domain deletion mutants, point mutagenesis of ICAM-4, molecular modeling, synthetic peptide inhibition, erythrophagocytosis inhibition assay Blood High 16985175
2007 Epinephrine-induced LW/ICAM-4 activation on sickle RBCs promotes vaso-occlusion in vivo. Epinephrine-treated human SS RBCs but not normal RBCs showed increased adhesion to murine endothelium and caused vaso-occlusion and organ sequestration after infusion into nude mice. This was prevented by the beta-adrenergic receptor antagonist propranolol or by soluble recombinant LW. Epinephrine activation occurs via beta-adrenergic receptor (beta-AR) stimulation. In vivo nude mouse infusion model with intravital microscopy, propranolol blockade, soluble recombinant LW competition, murine sickle RBC experiments Blood High 17609430
2012 Epinephrine increases both the frequency and strength of adhesion events between ICAM-4 on sickle cell trait erythrocytes and endothelial alphaVbeta3, as measured at the single-molecule level by atomic force microscopy. Single-molecule atomic force microscopy (AFM) force spectroscopy on sickle cell trait RBCs with and without epinephrine stimulation Biophysical journal Medium 22404936
2015 Gαs protein activation (downstream of beta2-adrenergic receptors) or Gαi inhibition increases SSRBC adhesion to endothelium via LW (ICAM-4) and CD44. The non-receptor tyrosine kinases p72(Syk) and p60-c-Src are more abundant in SSRBCs. LW physically interacts with activated p60-c-Src (demonstrated by co-immunoprecipitation), leading to LW tyrosine phosphorylation and SSRBC binding to endothelial alphaVbeta3. Cholera toxin (Gαs activation) and Pertussis toxin (Gαi inhibition) pharmacology, cell adhesion assays, co-immunoprecipitation of LW with p60-c-Src, phosphorylation detection The international journal of biochemistry & cell biology Medium 26007235
2017 ICAM-4 activation on RBCs is regulated by A-kinase anchoring proteins (AKAPs) via the cAMP-PKA signaling pathway. Epinephrine and forskolin (adenylyl cyclase activator) significantly increased the frequency of active ICAM-4 receptors on both normal and SS-RBCs without changing the unbinding force between ICAM-4 and alphaVbeta3. The baseline frequency of active ICAM-4 is not significantly different between normal and SS-RBCs. Single-molecule force spectroscopy (AFM), confocal microscopy, pharmacological modulation (epinephrine, forskolin, AKAP inhibitors) Biophysical journal Medium 28076805
2019 Valsartan (angiotensin II type 1 receptor (AT1R) blocker) decreases the surface density of active ICAM-4 receptors on RBCs and significantly impedes epinephrine-induced ICAM-4 activation on normal, sickle cell trait, and SS-RBCs, indicating cross-talk between the renin-angiotensin and beta-adrenergic signaling systems in regulating ICAM-4 activity on RBCs. Single-molecule force spectroscopy (AFM) measuring active ICAM-4 frequency on RBC membranes with and without valsartan and epinephrine PloS one Medium 31083675

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1986 Identification and partial characterization of the human erythrocyte membrane component(s) that express the antigens of the LW blood-group system. The Biochemical journal 118 2424433
2004 Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions. Blood 113 15308566
2006 Targeted gene deletion demonstrates that the cell adhesion molecule ICAM-4 is critical for erythroblastic island formation. Blood 107 16690966
1995 The red cell LW blood group protein is an intercellular adhesion molecule which binds to CD11/CD18 leukocyte integrins. European journal of immunology 93 8566017
2007 Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo. Blood 91 17609430
1994 The LW blood group glycoprotein is homologous to intercellular adhesion molecules. Proceedings of the National Academy of Sciences of the United States of America 84 8202485
2002 Red cell ICAM-4 is a novel ligand for platelet-activated alpha IIbbeta 3 integrin. The Journal of biological chemistry 81 12477717
2006 Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4. Blood 74 16985175
1997 Influence of isoflavones in soy protein isolates on development of induced prostate-related cancers in L-W rats. Nutrition and cancer 73 9200149
2000 Binding sites of leukocyte beta 2 integrins (LFA-1, Mac-1) on the human ICAM-4/LW blood group protein. The Journal of biological chemistry 57 10846180
2012 Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries. Annals of the rheumatic diseases 54 22523428
2003 Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to alpha V integrins. Blood 44 14551135
2006 Peptides based on alphaV-binding domains of erythrocyte ICAM-4 inhibit sickle red cell-endothelial interactions and vaso-occlusion in the microcirculation. American journal of physiology. Cell physiology 39 16738001
1999 Erythroid cell adhesion molecules Lutheran and LW in health and disease. Bailliere's best practice & research. Clinical haematology 37 10895261
2015 LW-213 induces G2/M cell cycle arrest through AKT/GSK3β/β-catenin signaling pathway in human breast cancer cells. Molecular carcinogenesis 36 25945460
2016 LW-AFC, a new formula derived from Liuwei Dihuang decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in PrP-hAβPPswe/PS1ΔE9 transgenic mice. Alzheimer's research & therapy 35 27964740
2002 Novel secreted isoform of adhesion molecule ICAM-4: potential regulator of membrane-associated ICAM-4 interactions. Blood 34 12406883
2012 Cloning and functional expression of an acidophilic β-mannanase gene (Anman5A) from Aspergillus niger LW-1 in Pichia pastoris. Journal of agricultural and food chemistry 30 22225502
2004 Integrin receptor specificity for human red cell ICAM-4 ligand. Critical residues for alphaIIbeta3 binding. European journal of biochemistry 29 15355350
2021 Cholesterol-associated lysosomal disorder triggers cell death of hematological malignancy: Dynamic analysis on cytotoxic effects of LW-218. Acta pharmaceutica Sinica. B 28 34729308
2013 LW-214, a newly synthesized flavonoid, induces intrinsic apoptosis pathway by down-regulating Trx-1 in MCF-7 human breast cells. Biochemical pharmacology 27 24374359
1989 Properties of the blood group LW glycoprotein and preliminary comparison with Rh proteins. Molecular immunology 25 2514351
2023 LW-213 induces immunogenic tumor cell death via ER stress mediated by lysosomal TRPML1. Cancer letters 24 37806516
1996 Characterization of the gene encoding the human LW blood group protein in LW+ and LW- phenotypes. Blood 24 8639917
1990 Surface orientation and antigen properties of Rh and LW polypeptides of the human erythrocyte membrane. The Journal of biological chemistry 24 1979326
2020 LW-213 induces cell apoptosis in human cutaneous T-cell lymphomas by activating PERK-eIF2α-ATF4-CHOP axis. Acta pharmacologica Sinica 23 32747719
2017 The Effects of LW-AFC on the Hippocampal Transcriptome in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer's Disease. Journal of Alzheimer's disease : JAD 22 28222521
2017 LW-215, a newly synthesized flavonoid, exhibits potent anti-angiogenic activity in vitro and in vivo. Gene 22 29196258
2012 Epinephrine modulates BCAM/Lu and ICAM-4 expression on the sickle cell trait red blood cell membrane. Biophysical journal 22 22404936
1984 Linkage of the LW blood group locus with the complement C3 and Lutheran blood group loci. Annals of human genetics 22 6431896
2016 Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity. Frontiers in neuroanatomy 21 27375437
2021 CRISPR/Cas9-mediated knockout of LW-opsin reduces the efficiency of phototaxis in the diamondback moth Plutella xylostella. Pest management science 20 33837633
2008 Role and regulation of sickle red cell interactions with other cells: ICAM-4 and other adhesion receptors. Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine 20 18502676
1998 Dihydrotestosterone prevents spontaneous adenocarcinomas in the prostate-seminal vesicle in aging L-W rats. The Prostate 20 9687988
1988 The chromosome 19 linkage group LDLR, C3, LW, APOC2, LU, SE in man. Annals of human genetics 20 2907851
2016 Selective cytotoxicity of microcystins LR, LW and LF in rat astrocytes. Toxicology letters 19 27864109
2019 Active fraction combination from Liuwei Dihuang decoction (LW-AFC) ameliorates corticosterone-induced long-term potentiation (LTP) impairment in mice in vivo. Journal of ethnopharmacology 16 30851370
2017 LW-AFC Effects on N-glycan Profile in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer's Disease. Aging and disease 16 28203484
1990 Comparative analysis by two-dimensional iodopeptide mapping of the RhD protein and LW glycoprotein. Blood 14 2112034
1982 A 'new' allele giving further insight into the LW blood group system. Vox sanguinis 14 6808767
2017 Regulation of Active ICAM-4 on Normal and Sickle Cell Disease RBCs via AKAPs Is Revealed by AFM. Biophysical journal 13 28076805
2017 LW-FQZip 2: a parallelized reference-based compression of FASTQ files. BMC bioinformatics 13 28320326
2006 LW protein: a promiscuous integrin receptor activated by adrenergic signaling. Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine 13 16564726
1975 A new example of anti-LW and further studies on heterogeneity of the system. Transfusion 13 809874
2015 Gαs proteins activate p72(Syk) and p60-c-Src tyrosine kinases to mediate sickle red blood cell adhesion to endothelium via LW-αvβ3 and CD44-CD44 interactions. The international journal of biochemistry & cell biology 10 26007235
2020 Nutritional support for lactating women with or without azithromycin for infants compared to breastfeeding counseling alone in improving the 6-month growth outcomes among infants of peri-urban slums in Karachi, Pakistan-the protocol for a multiarm assessor-blinded randomized controlled trial (Mumta LW trial). Trials 9 32873314
2019 LW-213, a newly synthesized flavonoid, induces G2/M phase arrest and apoptosis in chronic myeloid leukemia. Acta pharmacologica Sinica 9 31316178
1984 Restricted expression of LW antigen on subsets of human B and T lymphocytes. Journal of immunogenetics 8 6443217
2022 Insight into the Molecular Mechanism for the Discrepant Inhibition of Microcystins (MCLR, LA, LF, LW, LY) on Protein Phosphatase 2A. Toxins 7 35737051
2018 Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes. Glycoconjugate journal 7 29305779
2024 Inducing ubiquitination and degradation of TrxR1 protein by LW-216 promotes apoptosis in non-small cell lung cancer via triggering ROS production. Neoplasia (New York, N.Y.) 6 38733769
2022 A new high-prevalence LW antigen detected by an antibody in an Indigenous Australian homozygous for LW*A c.309C>A variant. Vox sanguinis 6 35412682
2014 Genetic variation of the whole ICAM4 gene in Caucasians and African Americans. Transfusion 6 24673173
1985 Long-term in vivo survival of Rh(D)-negative donor red cells in a patient with anti-LW. Transfusion 6 3918363
2024 LW-213, a derivative of wogonin, triggers reticulophagy-mediated cell death in NSCLC via lysosomal damage combined with NPC1 inhibition. Phytomedicine : international journal of phytotherapy and phytopharmacology 5 39241385
1992 Review: the LW blood group system. Immunohematology 5 15946068
1985 G-banding chromosome studies of acute lymphoblastic Lewis rat leukemia (KPH-Lw-I). Neoplasma 5 3873622
2019 Valsartan impedes epinephrine-induced ICAM-4 activation on normal, sickle cell trait and sickle cell disease red blood cells. PloS one 3 31083675
2025 UV2 and LW opsin genes mediate phototactic responses in the Asian lady beetle, Harmonia axyridis. Insect science 2 40931758
2014 Involvement of C/EBPβ in monocytic differentiation of acute myeloid leukemia cells induced by LW-218, a new synthesized flavonoid. Neoplasma 2 25150309
2008 [Polymorphism of LW blood group gene in Chinese population]. Zhongguo shi yan xue ye xue za zhi 2 18549656
1987 The LW:C3 recombination fraction in female meioses. Annals of human genetics 2 3120637
2025 Anti-LW masquerading as anti-D in a D+ patient. Immunohematology 1 40146180
2025 Is it anti-D or anti-LW? A brief synopsis of the biology of the LW blood group and the importance and differential laboratory methods to discriminate these specificities. Laboratory medicine 1 40413616
2024 LW-1 induced resistance to TMV in tobacco was mediated by nitric oxide and salicylic acid pathway. Pesticide biochemistry and physiology 1 38879345
2022 1H, 13C and 15N resonance assignments of TFIIS LW domain from Saccharomyces cerevisiae. Biomolecular NMR assignments 1 35060010
1996 LW/SO cell line: a tool for studying the phenotypical characterization and commitment of hematopoietic stem cells. Annals of hematology 1 8645743
2026 Bacillus velezensis LW-66: A Broad-Spectrum Biocontrol Agent Against Apple Tree Canker and Other Plant Fungal Diseases. Microorganisms 0 42075284
2025 LW-AFC Protects Against Neurological and Neuropsychiatric Effects of SARS-CoV-2 Spike Protein in Mice. Basic & clinical pharmacology & toxicology 0 40702776
2025 LW-PWDNet: a lightweight and cross-terrain adaptive framework for early pine wilt disease detection. Frontiers in plant science 0 41245450
2023 The LW blood group system: not just "tagging along" with D. Immunohematology 0 37405848
2023 DNA methylation of ICAM4 and NOXO1 participate in the formation of uterine fibroids via regulating immune cell infiltration. Cellular and molecular biology (Noisy-le-Grand, France) 0 38015525
2020 1H, 13C and 15N resonance assignments of TFIIS LW domain from Homo sapiens. Biomolecular NMR assignments 0 32361817
2014 Commentary on "the E3 ubiquitin ligase Siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activity." Qi J, Tripathi M, Mishra R, Sahgal N, Fazli L, Ettinger S, Placzek WJ, Claps G, Chung LW, Bowtell D, Gleave M, Bhowmick N, Ronai ZA, Signal Transduction Program, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.: Cancer Cell 2013;23(6):332-46. Urologic oncology 0 24445292

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