Affinage

CD36

Platelet glycoprotein 4 · UniProt P16671

Length
472 aa
Mass
53.1 kDa
Annotated
2026-06-09
100 papers in source corpus 26 papers cited in narrative 26 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

CD36 is a heavily glycosylated integral membrane scavenger receptor that functions as a multiligand sensor and transporter linking extracellular lipids and matrix proteins to intracellular signaling and metabolism (PMID:2468669, PMID:19471024). It engages structurally diverse ligands: collagen, where it mediates early platelet adhesion and activation (PMID:2468670); thrombospondin-1 (TSP-1), through a two-step CLESH-1/TSR-1 interaction that drives endothelial anti-angiogenic responses and, in AML blasts, lipid-uptake-independent migration and dissemination (PMID:1381367, PMID:12957861, PMID:37327406); oxidized LDL, which redirects macrophage mitochondrial metabolism toward superoxide production and NF-κB-driven inflammation (PMID:31625810); and long-chain fatty acids, which it transports into muscle, adipose, and other tissues, acting at the endothelium as a gatekeeper for tissue fatty acid uptake (PMID:15294038, PMID:30047927). Fatty acid uptake proceeds through a dynamic palmitoylation cycle: ligand binding activates LYN, which inactivates the palmitoyl acyltransferase DHHC5, permitting APT1-mediated depalmitoylation and SYK recruitment to initiate caveolae-dependent endocytosis (PMID:32958780). CD36 surface availability and stability are set by this palmitoylation cycling (also via DHHC6/SELENOK) and by UCHL1-mediated removal of K48-polyubiquitin that prevents proteasomal degradation (PMID:32801299, PMID:38320455). Through these activities CD36 couples lipid handling to metabolic and inflammatory programs: it enhances insulin receptor phosphorylation via Fyn (PMID:29748289), drives hepatocyte de novo lipogenesis by complexing with INSIG2 to free SCAP and activate SREBP1 (PMID:34974159), promotes adipogenesis and regulates adipocyte lipolysis through cAMP/PKA and Src-ERK signaling (PMID:22815385, PMID:22507268), and is required for megakaryocyte PUFA accumulation, proplatelet production, and normal platelet counts, with human loss-of-function mutations causing thrombocytopenia and bleeding (PMID:39195958). In platelets, CD36 signaling generates H2O2 that sulfenylates Src-family kinase cysteines to lower the activation threshold in dyslipidemia (PMID:32946569). CD36 also mediates phagocytic and endocytic internalization, taking up Plasmodium-infected erythrocytes and cooperating with TLRs (PMID:19864601, PMID:27073833), and routing large polar drugs and PROTACs through an EEA1/Rab5 endosomal cascade (PMID:40250420).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1989 High

    Established CD36/GPIV as a defined cell-surface glycoprotein and its first ligand, answering what the molecule is and how it engages collagen during platelet adhesion.

    Evidence Protein purification, Edman sequencing, and carbohydrate analysis plus direct collagen binding and platelet aggregation assays

    PMID:2468669 PMID:2468670

    Open questions at the time
    • Collagen-binding domain not mapped at residue level
    • Downstream platelet signaling from collagen engagement not defined
  2. 1992 High

    Resolved the molecular logic of CD36-thrombospondin-1 binding, showing a two-step conformational mechanism rather than a single-site interaction.

    Evidence Synthetic CD36 peptide competition and solid-phase TSP-1 binding with epitope mapping

    PMID:1381367

    Open questions at the time
    • Functional consequence of TSP-1 binding not addressed in this study
    • No structural validation of the two-step model
  3. 2003 Medium

    Identified CD36 as the endothelial TSP-1 receptor mediating anti-angiogenic signaling via the CLESH-1/TSR-1 interface, extending TSP-1 binding to vascular biology.

    Evidence Domain structure-function analysis, competition binding, and in vivo angiogenesis models (review of primary work)

    PMID:12957861

    Open questions at the time
    • Review summary rather than single primary dataset
    • Intracellular signaling from CLESH-1 engagement not detailed
  4. 2004 Medium

    Defined CD36 as a regulated fatty acid transporter, showing acute insulin/contraction-driven translocation from intracellular depots to the plasma membrane.

    Evidence Null/overexpression studies, subcellular fractionation, and radiolabeled FA uptake in muscle (review)

    PMID:15294038

    Open questions at the time
    • Molecular machinery of translocation not identified
    • Direct fatty acid transport mechanism vs. facilitated uptake unresolved
  5. 2009 Medium

    Outlined the CD36 signaling apparatus—Src-family kinases, MAP kinases, Vav GEFs, and ROS within lipid rafts—linking ligand binding to intracellular cascades.

    Evidence Co-IP, fractionation, and genetic/pharmacological perturbation (review)

    PMID:19471024

    Open questions at the time
    • Ligand-specific signaling specificity not delineated
    • Direct kinase recruitment mechanism unresolved
  6. 2009 High

    Showed CD36 mediates phagocytic uptake of parasitized erythrocytes but requires TLR cooperation for cytokine output, separating internalization from inflammatory signaling.

    Evidence Antibody-induced endocytosis and phagocytosis assays in TLR2/IRAK4-deficient primary macrophages

    PMID:19864601

    Open questions at the time
    • Molecular basis of CD36-TLR cooperation not defined
    • Endocytic machinery for PE uptake not mapped
  7. 2012 High

    Connected CD36 to adipocyte biology, showing it both promotes adipogenesis and modulates lipolysis through cAMP/PKA and Src-ERK pathways with trafficking feedback.

    Evidence siRNA knockdown, CD36-null mice, pharmacological inhibitor, and phosphorylation/trafficking assays in adipocytes

    PMID:22507268 PMID:22815385

    Open questions at the time
    • Direct link between FA transport and lipolytic signaling unresolved
    • How CD36 controls cAMP levels mechanistically unclear
  8. 2018 High

    Distinguished cell-type-specific CD36 functions: endothelial CD36 gates tissue FA uptake while muscle CD36 enhances insulin receptor signaling via Fyn.

    Evidence Cell-specific Cre-lox KO, [11C]palmitate PET, metabolic phenotyping, Co-IP of CD36 with IR, and Fyn kinase assays

    PMID:29748289 PMID:30047927

    Open questions at the time
    • Mechanism by which endothelial CD36 transfers FA to parenchyma not defined
    • How fatty acid saturation tunes the CD36-Fyn-IR axis mechanistically unclear
  9. 2019 High

    Revealed that oxLDL-CD36 drives a macrophage mitochondrial switch from OXPHOS to superoxide production, mechanistically linking scavenger receptor uptake to chronic inflammation.

    Evidence RNA-seq, lipidomics, metabolic flux, imaging, and NF-κB assays in Apoe-null high-fat-diet model

    PMID:31625810

    Open questions at the time
    • Direct effector linking CD36 to ATP5A inhibition not identified
    • Whether the switch is reversible in vivo unresolved
  10. 2020 High

    Defined the dynamic palmitoylation cycle as the engine of CD36 fatty acid uptake, with LYN-DHHC5-APT1-SYK controlling caveolae-dependent endocytosis.

    Evidence Co-IP, site-specific phosphorylation mapping (DHHC5 Tyr91), APT1/LYN/SYK inhibition, and in vivo validation

    PMID:32958780

    Open questions at the time
    • Structural basis of palmitoylation-dependent conformational change unknown
    • How FA binding is transduced to LYN activation not resolved
  11. 2020 High

    Identified post-translational control of CD36 abundance—platelet redox signaling via Src sulfenylation and UCHL1 deubiquitination stabilizing CD36 against proteasomal degradation.

    Evidence Cysteine sulfenic acid chemical probes and platelet/thrombosis assays; UCHL1 KD/inhibition with K48-ubiquitin and protein/mRNA quantification

    PMID:32801299 PMID:32946569

    Open questions at the time
    • UCHL1 finding rests on a single lab without reciprocal validation
    • E3 ligase placing K48 chains on CD36 not identified
  12. 2021 High

    Placed hepatocyte CD36 upstream of SREBP1-driven lipogenesis through an INSIG2-disrupting complex, and identified a CD36+ Kupffer cell subset driving steatosis-associated oxidative stress.

    Evidence Hepatocyte-specific KO, Co-IP, proximity ligation, and SCAP-INSIG rescue; single-cell profiling with targeted Cd36 silencing in KC2

    PMID:34469775 PMID:34974159

    Open questions at the time
    • How a surface receptor accesses ER-resident INSIG2 not explained
    • KC2 oxidative stress mechanism only Medium-confidence
  13. 2023 Medium

    Extended CD36's reach to ubiquitin regulation of partner proteins and to lipid-uptake-independent functions, including FSP1 destabilization in ferroptosis and TSP-1-driven AML migration.

    Evidence LC-MS/MS, Co-IP, ubiquitination site mapping, and KO/xenograft models

    PMID:36878933 PMID:37327406 PMID:37588197

    Open questions at the time
    • How CD36 directs ubiquitination of FSP1 mechanistically unclear
    • Each finding from a single lab without independent replication
  14. 2024 Medium

    Linked SELENOK and DHHC6 to CD36 palmitoylation in microglia, controlling membrane localization required for Aβ phagocytosis in an Alzheimer's model.

    Evidence SELENOK KO/OE, DHHC6 palmitoylation assays, microglial phagocytosis, and human brain validation in 5xFAD mice

    PMID:38320455

    Open questions at the time
    • Single lab; reciprocal validation lacking
    • Relationship between DHHC6 and the DHHC5/APT1 cycle not integrated
  15. 2025 High

    Established CD36 as an uptake route for large polar small molecules and PROTACs through an EEA1/Rab5 endosomal cascade, opening a pharmacological exploitation of the receptor.

    Evidence Biotinylated probe target fishing, CD36 KD/KI, endosomal co-localization, and in vivo PROTAC efficacy with medicinal chemistry

    PMID:40250420

    Open questions at the time
    • Binding determinants distinguishing drug cargo from lipid ligands not defined
    • Relationship to caveolae-dependent FA endocytosis route unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD36's single receptor architecture selects among structurally unrelated ligands and routes each to distinct signaling, metabolic, endocytic, or ubiquitin-regulatory outcomes remains unresolved.
  • No structural model coupling ligand identity to downstream pathway choice
  • How palmitoylation, ubiquitination, and redox modifications are coordinated in vivo unknown
  • Whether distinct internalization routes (caveolae vs. EEA1/Rab5) reflect distinct ligand classes unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0038024 cargo receptor activity 4 GO:0005215 transporter activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005739 mitochondrion 2 GO:0005768 endosome 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-109582 Hemostasis 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
AIFM2FYNINSIG2INSRLYNSYKTHBS1UCHL1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 CD36 (GPIV) directly binds collagen Type I fibrils with high affinity (Kd ~0.34 nM) and mediates the early stages of platelet adhesion and activation in response to collagen, as demonstrated by competitive inhibition with purified GPIV and Fab fragments of anti-GPIV antibody blocking collagen-induced shape change, aggregation, and secretion. Direct binding assay of purified GPIV to collagen fibrils; competitive inhibition with purified GPIV and Fab fragments of polyclonal anti-GPIV antibody; platelet adhesion/aggregation assays The Journal of biological chemistry High 2468670
1989 CD36 (GPIV) is a heavily O- and N-glycosylated integral membrane glycoprotein (~88 kDa, 26% carbohydrate) with an N-terminal hydrophilic domain followed by a transmembrane domain, as determined by amino acid sequencing (first 36 residues via Edman degradation), carbohydrate composition analysis, and surface localization confirmed by flow cytometry and immunoprecipitation. Protein purification, Edman degradation N-terminal sequencing, carbohydrate composition analysis, flow cytometry, immunoprecipitation, radiolabeling The Journal of biological chemistry High 2468669
1992 CD36-thrombospondin-1 (TSP-1) interaction occurs via a two-step mechanism: the CD36 sequence 139–155 binds first to TSP-1, inducing a conformational change that exposes a second high-affinity site on TSP-1 that then engages CD36 sequence 93–110. Peptide 139–155 augments rather than inhibits CD36-TSP binding, while peptide 93–110 blocks it. Synthetic CD36 peptide competition assays; solid-phase TSP binding; OKM5 epitope mapping; platelet aggregation assays The Journal of biological chemistry High 1381367
2003 CD36 is the endothelial cell receptor for thrombospondin-1 (TSP-1) and mediates its anti-angiogenic activity. Binding is mediated by the TSP type I repeat (TSR-1) domain of TSP-1 interacting with a conserved domain called CLESH-1 in CD36. Histidine-rich glycoprotein (HRGP) acts as a soluble decoy blocking TSP-1 binding to CD36, thereby inhibiting the anti-angiogenic response. Structure-function analysis of TSP-1 and CD36 domains; competition binding experiments; in vivo angiogenesis models Frontiers in bioscience : a journal and virtual library Medium 12957861
2004 CD36/FAT regulates fatty acid transport into cardiac and skeletal muscle cells; null mutation reduces FA uptake and metabolism while overexpression increases it. CD36 is also localized on the mitochondrial membrane and participates in FA transport across the mitochondrial membrane. Insulin and muscle contraction acutely translocate CD36 from an intracellular depot to the plasma membrane within minutes to increase FA transport. Genetic null mutation and overexpression studies; subcellular fractionation showing mitochondrial localization; radiolabeled FA uptake assays; insulin/contraction stimulation experiments in muscle The Proceedings of the Nutrition Society Medium 15294038
2009 CD36 ligand-dependent signaling involves recruitment and activation of non-receptor tyrosine kinases (Src family), specific MAP kinases, and Vav family guanine nucleotide exchange factors; modulation of focal adhesion constituents; and generation of intracellular reactive oxygen species. CD36 is localized in cholesterol-rich membrane microdomains (lipid rafts) and interacts with tetraspanins and integrins. Biochemical signaling studies; co-immunoprecipitation; subcellular fractionation; genetic and pharmacological perturbation of signaling components Science signaling Medium 19471024
2009 CD36 mediates phagocytic internalization of Plasmodium falciparum-parasitized erythrocytes (PEs) by macrophages independently of TLR2 or IRAK4 signaling. Selective CD36 engagement does not by itself produce proinflammatory cytokines; however, TLR agonist pretreatment markedly enhances CD36-mediated particle uptake, indicating CD36 must cooperate with TLRs for cytokine responses. Antibody-induced CD36 endocytosis; phagocytosis assays with PEs in primary human and murine macrophages; TLR2/IRAK4-deficient macrophages; cytokine measurement Journal of immunology High 19864601
2012 CD36 regulates adipocyte lipolysis by modulating cAMP levels and PKA-dependent phosphorylation of hormone-sensitive lipase (HSL) and perilipin. CD36 knockdown decreased lipolysis induced by β-adrenergic, adenylyl cyclase, and PDE inhibitor stimulation, and this was partially mediated through the Src-ERK1/2 pathway. Isoproterenol-induced CD36 internalization was blocked by HSL inhibition, revealing feedback regulation of lipolysis via CD36 trafficking. siRNA knockdown in 3T3-L1 adipocytes; cAMP measurement; HSL and perilipin phosphorylation assays; CD36-null mice; plasma membrane-impermeable CD36 inhibitor (sulfo-N-succinimidyl oleate); live-cell CD36 trafficking assays FASEB journal High 22815385
2012 CD36 promotes adipocyte differentiation (adipogenesis) in vitro and in vivo; CD36 gene silencing impairs preadipocyte differentiation, reduces de novo fat pad formation in nude mice, and CD36-deficient mice have lower adipose tissue mass in diet-induced obesity. CD36 siRNA knockdown in 3T3-F442A preadipocytes; Oil Red O staining; adipogenic marker expression; in vivo fat pad formation assay in NUDE mice; nutritional obesity model in CD36 KO mice Biochimica et biophysica acta High 22507268
2018 Endothelial cell (EC)-specific, but not parenchymal cell (myocyte/adipocyte)-specific, CD36 deletion acts as a gatekeeper for tissue fatty acid uptake. EC-CD36 KO mice had increased fasting plasma FAs, reduced radiolabeled long-chain FA uptake into heart, skeletal muscle, and brown adipose tissue (confirmed by [11C]palmitate PET), and improved glucose tolerance and insulin sensitivity on high-fat diet. Cell-specific Cre-lox deletion; radiolabeled FA uptake assays; [11C]palmitate PET imaging; plasma FA/TG measurements; glucose/insulin tolerance tests The Journal of clinical investigation High 30047927
2018 CD36 promotes insulin receptor (IR) tyrosine phosphorylation via functional interaction with Fyn kinase, and recruits p85 to enhance downstream insulin signaling. CD36 deletion in skeletal muscle reduces ceramide levels but impairs meal-associated glucose disposal. Pretreatment with saturated fatty acids suppresses CD36-Fyn enhancement of IR phosphorylation, while unsaturated fatty acids are neutral or stimulatory. Skeletal muscle-specific CD36 KO mice; primary human myotube CD36 depletion; co-immunoprecipitation of CD36 with IR; Fyn kinase phosphorylation assays; ceramide measurement; glucose disposal during meals Diabetes High 29748289
2019 CD36 mediates a mitochondrial metabolic switch in macrophages from oxidative phosphorylation to superoxide production in response to oxidized LDL. OxLDL via CD36 upregulates long-chain FA uptake and mitochondrial import effectors while downregulating FA oxidation and inhibiting ATP5A (an ETC component), leading to FA accumulation, mitochondrial structural changes, superoxide production, and NF-κB activation driving chronic inflammation. RNA sequencing; flow cytometry; 3H-palmitic acid uptake; lipidomics; confocal and electron microscopy; functional energetics (mitochondria-specific superoxide inhibition); NF-κB activation assays; Apoe-null high-fat diet mouse model Circulation research High 31625810
2020 Fatty acid binding to CD36 activates the downstream kinase LYN, which phosphorylates DHHC5 (a palmitoyl acyltransferase) at Tyr91, inactivating it. CD36 then undergoes depalmitoylation by APT1 and recruits SYK kinase to phosphorylate JNK and VAV proteins, initiating caveolae-dependent endocytic uptake of fatty acids. Dynamic palmitoylation cycling (palmitoylation/depalmitoylation) is required for CD36-mediated FA uptake; blocking endocytosis by inhibiting APT1, LYN, or SYK abolishes CD36-dependent FA uptake and lipid droplet growth. Co-immunoprecipitation; kinase assays; site-specific phosphorylation analysis (DHHC5 Tyr91); APT1/LYN/SYK inhibition; caveolae-dependent internalization assays; palmitoylation state manipulation; high-fat-diet mouse model Nature communications High 32958780
2020 CD36 signaling in platelets generates hydrogen peroxide flux that promotes cysteine sulfenylation of Src family kinases, activating them and lowering the threshold for platelet activation in dyslipidemia. Selective inhibition of cysteine sulfenylation with carbon nucleophiles inhibited CD36-mediated platelet aggregation and procoagulant phosphatidylserine externalization, and rescued enhanced arterial thrombosis in dyslipidemic mice. Carbon nucleophile-based cysteine sulfenic acid detection; CD36-blocking antibody; enzymatic H2O2 degradation; platelet aggregation assays; phosphatidylserine externalization assay; in vivo arterial thrombosis model in dyslipidemic mice Blood advances High 32946569
2020 Deubiquitinase UCHL1 stabilizes CD36 protein by removing K48-polyubiquitin chains from CD36, preventing its proteasomal degradation. UCHL1 inhibition or deletion increases K48-polyubiquitin on CD36, reduces CD36 protein (but not mRNA), decreases oxLDL uptake, and reduces foam cell formation. UCHL1 siRNA/inhibitor treatment; ubiquitination analysis (K48-polyubiquitin); co-immunoprecipitation; CD36 protein and mRNA quantification; lipid accumulation assays Cell death & disease Medium 32801299
2021 Hepatocyte CD36 promotes de novo lipogenesis (DNL) by forming a complex with INSIG2 that disrupts the SCAP-INSIG2 interaction, thereby releasing SCAP to escort SREBP1 from ER to Golgi for processing and activation. CD36-knockout hepatocytes show reduced SREBP1 and downstream lipogenic enzymes (FASN, ACCα, ACLY), while CD36 overexpression stimulates insulin-mediated DNL. Hepatocyte-specific CD36 KO mice; co-immunoprecipitation; proximity ligation assay (INSIG2-SCAP-CD36 interaction); RNA sequencing; lipid deposition and DNL measurement; INSIG2-SCAP interaction rescue with 25-hydroxycholesterol/betulin Molecular metabolism High 34974159
2021 A subset of Kupffer cells (KC2) expressing CD36 contributes to liver oxidative stress in obesity-associated hepatic steatosis. Targeted silencing of Cd36 specifically in KC2 reduces liver oxidative stress associated with obesity, demonstrating a cell-autonomous metabolic function of CD36 in this Kupffer cell subpopulation. High-dimensional single-cell profiling; KC2 depletion and targeted Cd36 silencing; oxidative stress measurement in diet-induced obesity mouse model Immunity Medium 34469775
2023 CD36 binds to FSP1 (ferroptosis suppressor protein 1) and regulates its ubiquitination at K16 and K24, leading to FSP1 degradation and progression of ferroptosis in renal proximal tubular cells. CD36 deletion in mice increases ROS accumulation, ferroptosis activation, and acute kidney injury, identifying CD36 as a regulator of FSP1 stability. LC-MS/MS; co-immunoprecipitation; ubiquitination site mapping (K16, K24 of FSP1); CD36-null mice; cisplatin-induced AKI model Genes & diseases Medium 37588197
2023 CD36 promotes blast migration and extramedullary dissemination in AML via its interaction with thrombospondin-1, not through lipid uptake. CD36 was dispensable for lipid uptake in AML blasts but was required for TSP-1-driven migration. CD36 inhibition reduced metastasis in xenograft models and prolonged survival of chemotherapy-treated mice. CD36 inhibition in xenograft mouse models; TSP-1 binding assays; lipid uptake assays (showing CD36 dispensable); patient cohort correlation Cancer research Medium 37327406
2024 SELENOK (selenoprotein K) regulates CD36 palmitoylation through DHHC6, controlling CD36 localization to the microglial plasma membrane and thereby enabling Aβ phagocytosis. SELENOK deficiency reduces CD36 palmitoylation, impairs CD36 membrane localization, and inhibits microglial Aβ phagocytosis, exacerbating cognitive deficits in 5xFAD AD mice. In vivo 5xFAD mouse model with SELENOK KO/OE; DHHC6 palmitoylation assays; CD36 palmitoylation measurement in AD patient and mouse brains; microglial phagocytosis assays; Aβ quantification Redox biology Medium 38320455
2025 CD36 binds diverse large/polar small-molecule drugs and PROTACs and facilitates their cellular uptake via CD36-mediated EEA1/Rab5-positive early endosomal cascade. Chemical modification of PROTACs to enhance CD36 binding (via prodrug approach) markedly enhances their anti-tumor efficacy by augmenting permeability and solubility. Biotinylated chemical-probe target fishing; genetic knockdown/knockin of CD36; endosomal co-localization (EEA1/Rab5 markers); in vitro and in vivo PROTAC uptake and efficacy assays Cell High 40250420
2023 CD36 in cancer-associated fibroblasts (CAFs) mediates oxidized LDL uptake, triggering lipid peroxidation/p38/C/EBPs-dependent MIF expression. The secreted MIF recruits CD33+ myeloid-derived suppressor cells (MDSCs) in a MIF- and CD74-dependent manner to create an immunosuppressive tumor microenvironment. CD36 inhibition synergizes with anti-PD-1 immunotherapy in HCC models. Lineage-tracing; CD36 inhibitor + oxLDL uptake assays; lipid peroxidation assays; p38/C/EBP pathway analysis; MDSC recruitment assays; co-implantation in vivo HCC model; anti-PD-1 combination treatment Cell discovery Medium 36878933
2015 TSP-1 interaction with CD36 on podocytes mediates free fatty acid (FFA)-induced podocyte apoptosis via a TGF-β-independent mechanism. FFA stimulates TSP-1 expression via MAPK pathway activation; blocking TSP-1-CD36 binding with a peptide attenuated FFA-induced podocyte apoptosis. In vivo, both TSP1-deficient and CD36-deficient mice showed attenuated obesity-associated podocyte apoptosis and dysfunction. Peptide blockade of TSP1-CD36 binding; TSP1 KO and CD36 KO mouse diet-induced obesity models; podocyte apoptosis assays; MAPK pathway analysis; TGF-β independence confirmed Biochimica et biophysica acta Medium 25835637
2020 Endothelial CD36 deficiency prevents normal angiogenesis and vascular repair after ischemia. Oleic acid (OA) increases EC migration and wound healing in a CD36-dependent manner. CD36 knockdown abolished OA-induced increases in phospho-AMPK, and EC-specific CD36 KO mice had reduced blood flow recovery and reduced CD31/MMP9 upregulation post-hindlimb ischemia. siRNA and antisense oligonucleotide CD36 KD; EC migration/wound healing assays; transwell migration; phospho-AMPK measurement; EC-specific CD36 KO mice; laser Doppler imaging post-ischemia; CD31 and MMP9 expression American journal of translational research Medium 33437358
2016 CD36 differentially regulates macrophage responses to smooth (S-LPS) versus rough (R-LPS) lipopolysaccharide. CD36 can substitute for CD14 in loading R-LPS onto TLR4/MD-2 enabling CD14-independent responses. CD36 promotes TRIF-dependent TLR4 signaling by facilitating TLR4/MD-2 endocytosis for both LPS chemotypes, while negatively regulating MyD88-dependent S-LPS signaling in the presence of serum by mediating internalization of S-LPS/CD14 complexes. CD14-deficient and CD36-deficient macrophages; LPS binding and TLR4/MD-2 loading assays; endocytosis assays; MyD88- and TRIF-dependent signaling measurement; serum/serum-free conditions PloS one Medium 27073833
2023 CD36 is required for efficient megakaryocyte differentiation, proplatelet production, and normal platelet counts. CD36 deletion in mice results in thrombocytopenia, and patients with CD36 loss-of-function mutations exhibit thrombocytopenia and increased bleeding. Megakaryocyte PUFA-containing phospholipid accumulation is largely dependent on CD36-mediated fatty acid uptake. CD36 KO mice; dietary PUFA/saturated FA manipulation; platelet count measurement; lipidome analysis of megakaryocytes and platelets; human CD36 loss-of-function patient analysis Nature cardiovascular research High 39195958

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Science signaling 973 19471024
1989 Identification of glycoprotein IV (CD36) as a primary receptor for platelet-collagen adhesion. The Journal of biological chemistry 441 2468670
2014 CD36, a scavenger receptor implicated in atherosclerosis. Experimental & molecular medicine 420 24903227
2020 CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis. Nature communications 356 32958780
2007 CD36 and macrophages in atherosclerosis. Cardiovascular research 301 17442283
2023 CD36+ cancer-associated fibroblasts provide immunosuppressive microenvironment for hepatocellular carcinoma via secretion of macrophage migration inhibitory factor. Cell discovery 300 36878933
2019 CD36 tango in cancer: signaling pathways and functions. Theranostics 291 31410189
2017 CD36 in chronic kidney disease: novel insights and therapeutic opportunities. Nature reviews. Nephrology 230 28919632
2022 The role of CD36 in cardiovascular disease. Cardiovascular research 222 33210138
2019 Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses. Circulation research 217 31625810
2018 Endothelial cell CD36 optimizes tissue fatty acid uptake. The Journal of clinical investigation 206 30047927
1989 Isolation and characterization of platelet glycoprotein IV (CD36). The Journal of biological chemistry 200 2468669
2007 CD36: implications in cardiovascular disease. The international journal of biochemistry & cell biology 191 17466567
2009 The minor envelope glycoproteins GP2a and GP4 of porcine reproductive and respiratory syndrome virus interact with the receptor CD163. Journal of virology 190 19939927
2021 A subset of Kupffer cells regulates metabolism through the expression of CD36. Immunity 187 34469775
2021 CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing. Molecular metabolism 164 34974159
2004 Regulation of fatty acid transport by fatty acid translocase/CD36. The Proceedings of the Nutrition Society 157 15294038
1996 Regulation of monocyte CD36 and thrombospondin-1 expression by soluble mediators. Arteriosclerosis, thrombosis, and vascular biology 155 8696941
1990 A platelet membrane glycoprotein (GP) deficiency in healthy blood donors: Naka- platelets lack detectable GPIV (CD36). Blood 144 1699620
2018 The CD36-PPARγ Pathway in Metabolic Disorders. International journal of molecular sciences 142 29883404
2009 CD36 regulates oxidative stress and inflammation in hypercholesterolemic CKD. Journal of the American Society of Nephrology : JASN 127 19211715
1992 Receptor properties of two varicella-zoster virus glycoproteins, gpI and gpIV, homologous to herpes simplex virus gE and gI. Journal of virology 124 1316474
2019 Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1. International journal of molecular medicine 118 31524223
2011 CD36 as a lipid sensor. Physiology & behavior 118 21354192
2018 CD36 and lipid metabolism in the evolution of atherosclerosis. British medical bulletin 116 29534172
2013 Innate immunity receptor CD36 promotes cerebral amyloid angiopathy. Proceedings of the National Academy of Sciences of the United States of America 111 23382216
2001 Role of CD36, the macrophage class B scavenger receptor, in atherosclerosis. Annals of the New York Academy of Sciences 111 11795270
2020 CD36 in Atherosclerosis: Pathophysiological Mechanisms and Therapeutic Implications. Current atherosclerosis reports 107 32772254
2003 Pathophysiology of human genetic CD36 deficiency. Trends in cardiovascular medicine 107 12732446
2022 CD36 favours fat sensing and transport to govern lipid metabolism. Progress in lipid research 106 36055468
2007 Molecular basis of human CD36 gene mutations. Molecular medicine (Cambridge, Mass.) 103 17673938
2000 CD36 and atherosclerosis. Current opinion in lipidology 103 11048891
2019 Apigenin inhibits STAT3/CD36 signaling axis and reduces visceral obesity. Pharmacological research 101 31877350
2018 Prolactin improves hepatic steatosis via CD36 pathway. Journal of hepatology 97 29452209
1997 Posttranslational processing and identification of a neutralization domain of the GP4 protein encoded by ORF4 of Lelystad virus. Journal of virology 94 9223499
2016 CD36 actions in the heart: Lipids, calcium, inflammation, repair and more? Biochimica et biophysica acta 91 27004753
2012 CD36 promotes adipocyte differentiation and adipogenesis. Biochimica et biophysica acta 88 22507268
2009 CD36 and TLR interactions in inflammation and phagocytosis: implications for malaria. Journal of immunology (Baltimore, Md. : 1950) 86 19864601
2011 CD36 genetics and the metabolic complications of obesity. Current opinion in clinical nutrition and metabolic care 85 21912245
2009 Inflammation, atherosclerosis, and arterial thrombosis: role of the scavenger receptor CD36. Cleveland Clinic journal of medicine 85 19376978
2022 Role of CD36 in cancer progression, stemness, and targeting. Frontiers in cell and developmental biology 83 36568966
1992 CD36 peptides enhance or inhibit CD36-thrombospondin binding. A two-step process of ligand-receptor interaction. The Journal of biological chemistry 78 1381367
2000 Expression of thrombospondin-1 and its receptor CD36 in human osteoarthritic cartilage. Annals of the rheumatic diseases 75 10834862
2012 PKCδ signalling regulates SR-A and CD36 expression and foam cell formation. Cardiovascular research 64 22687273
2008 Fisetin, morin and myricetin attenuate CD36 expression and oxLDL uptake in U937-derived macrophages. Biochimica et biophysica acta 64 18662803
2000 CD36 in atherosclerosis. The role of a class B macrophage scavenger receptor. Annals of the New York Academy of Sciences 64 10865832
2012 CD36 level and trafficking are determinants of lipolysis in adipocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 63 22815385
2003 CD36: a critical anti-angiogenic receptor. Frontiers in bioscience : a journal and virtual library 63 12957861
2012 CD36 inhibitors reduce postprandial hypertriglyceridemia and protect against diabetic dyslipidemia and atherosclerosis. PloS one 57 22662181
2018 Regulation of Insulin Receptor Pathway and Glucose Metabolism by CD36 Signaling. Diabetes 56 29748289
2011 CD36 as a multiple-ligand signaling receptor in atherothrombosis. Cardiovascular & hematological agents in medicinal chemistry 55 20939828
2019 Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma. Annals of surgical oncology 54 31605325
2024 Interplay of CD36, autophagy, and lipid metabolism: insights into cancer progression. Metabolism: clinical and experimental 52 38548128
2023 CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia. Cancer research 51 37327406
2023 CD36 promotes tubular ferroptosis by regulating the ubiquitination of FSP1 in acute kidney injury. Genes & diseases 49 37588197
2019 CD36 signaling in vascular redox stress. Free radical biology & medicine 49 30825500
2017 The role of CD36 receptor in the pathogenesis of atherosclerosis. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 48 28691408
2006 Binding-induced stabilization and assembly of the phage P22 tail accessory factor gp4. Journal of molecular biology 46 16970964
2014 The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis. Reproductive biology and endocrinology : RB&E 45 24628875
2008 Enhanced immune responses of mice inoculated recombinant adenoviruses expressing GP5 by fusion with GP3 and/or GP4 of PRRS virus. Virus research 45 18538882
2020 Deubiquitination of CD36 by UCHL1 promotes foam cell formation. Cell death & disease 42 32801299
2012 CD36 as a therapeutic target for endothelial dysfunction in stroke. Current pharmaceutical design 42 22574985
2022 The Past and Present Lives of the Intraocular Transmembrane Protein CD36. Cells 41 36611964
2021 CD36 - A novel molecular target in the neurovascular unit. The European journal of neuroscience 41 33560561
1992 Specific lysis of targets expressing varicella-zoster virus gpI or gpIV by CD4+ human T-cell clones. Journal of virology 40 1348545
2014 CD36 and malaria: friends or foes? A decade of data provides some answers. Trends in parasitology 39 25113859
2025 CD36-mediated endocytosis of proteolysis-targeting chimeras. Cell 38 40250420
2005 Expression of scavenger receptor CD36 in chronic renal failure patients. Artificial organs 38 16048476
2012 CD36 and taste of fat. Current opinion in clinical nutrition and metabolic care 36 22248592
2011 Soluble CD36- a marker of the (pathophysiological) role of CD36 in the metabolic syndrome? Archives of physiology and biochemistry 36 21250778
2021 CD36 Signaling in Diabetic Cardiomyopathy. Aging and disease 35 34094645
2024 CD36: The Bridge between Lipids and Tumors. Molecules (Basel, Switzerland) 34 38276607
2022 CD36 and Its Role in Regulating the Tumor Microenvironment. Current oncology (Toronto, Ont.) 34 36354702
2021 CD36 Senses Dietary Lipids and Regulates Lipids Homeostasis in the Intestine. Frontiers in physiology 34 33995128
2018 Blocking Wnt5a signaling decreases CD36 expression and foam cell formation in atherosclerosis. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 34 29474941
2007 CD36-TSP-HRGP interactions in the regulation of angiogenesis. Current pharmaceutical design 34 18220792
2024 Role of CD36 in central nervous system diseases. Neural regeneration research 32 37721278
2023 FOXO1 regulates the formation of bovine fat by targeting CD36 and STEAP4. International journal of biological macromolecules 32 37506793
2021 Ochratoxin A Induces Steatosis via PPARγ-CD36 Axis. Toxins 29 34822586
2020 Cysteine sulfenylation by CD36 signaling promotes arterial thrombosis in dyslipidemia. Blood advances 29 32946569
2020 CD36 and CD97 in Pancreatic Cancer versus Other Malignancies. International journal of molecular sciences 28 32781778
2023 Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36. Nature cardiovascular research 27 39195958
2020 Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis. International journal of molecular sciences 27 33028031
2018 Hypermethylated CD36 gene affected the progression of lung cancer. Gene 27 29969695
2015 Interaction of thrombospondin1 and CD36 contributes to obesity-associated podocytopathy. Biochimica et biophysica acta 27 25835637
2006 The role of hyperglycemia in FAT/CD36 expression and function. Pediatric surgery international 27 16838191
2005 CD36: a multiligand molecule. Laboratory hematology : official publication of the International Society for Laboratory Hematology 27 15790550
2015 Wnt1 positively regulates CD36 expression via TCF4 and PPAR-γ in macrophages. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 25721714
2009 CD36: a multi-modal target for acute stroke therapy. Journal of neurochemistry 26 19393018
2004 CD36 expression and brain function: does CD36 deficiency impact learning ability? Prostaglandins & other lipid mediators 24 16099393
2024 SELENOK-dependent CD36 palmitoylation regulates microglial functions and Aβ phagocytosis. Redox biology 23 38320455
1993 Expression of GPIV and N(aka) antigen on monocytes in N(aka)-negative subjects whose platelets lack GPIV. British journal of haematology 23 7692927
2020 Endothelial cell CD36 deficiency prevents normal angiogenesis and vascular repair. American journal of translational research 22 33437358
2021 Endothelial Cell CD36 Reduces Atherosclerosis and Controls Systemic Metabolism. Frontiers in cardiovascular medicine 21 34888367
2016 CD36 Differently Regulates Macrophage Responses to Smooth and Rough Lipopolysaccharide. PloS one 21 27073833
2023 CD36 as a double-edged sword in cancer. Immunology letters 20 38122906
2022 HIF-2α-induced upregulation of CD36 promotes the development of ccRCC. Experimental cell research 20 36252650
2019 Hyperoxidized Albumin Modulates Platelets and Promotes Inflammation Through CD36 Receptor in Severe Alcoholic Hepatitis. Hepatology communications 20 31909355
2022 CD36-A Host Receptor Necessary for Malaria Parasites to Establish and Maintain Infection. Microorganisms 19 36557610
2019 CD36- and obesity-associated granulosa cells dysfunction. Reproduction, fertility, and development 19 30832758

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