CD36-containing Thrombospondin-1 receptor complex (CD36-TSP-1 complex)

The CD36-containing Thrombospondin-1 (TSP-1) receptor complex is a multi-protein assembly on the cell surface that mediates the anti-angiogenic and pro-apoptotic effects of the matricellular protein Thrombospondin-1 (NIH, 2012). CD36, a scavenger receptor also known as fatty acid translocase (FAT), binds to the thrombospondin type 1 repeats (TSRs) of TSP-1, initiating a signaling cascade that involves the recruitment of Src-family kinases like Fyn and the activation of p38 MAPK and JNK, ultimately leading to endothelial cell apoptosis (AHA Journals, 2014). In microvascular endothelial cells, this complex often associates with Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and beta-1 integrins, where it recruits the phosphatase SHP-1 to dephosphorylate and inhibit VEGFR2 signaling, thereby antagonizing pro-angiogenic growth factors (Blood, 2013). Beyond its role in angiogenesis, the complex is involved in macrophage phagocytosis of apoptotic cells and platelet-mediated thrombus stabilization (ResearchGate, 2024). Therapeutic targeting of this complex has primarily focused on TSP-1 mimetic peptides, such as ABT-510 and ABT-898, which were developed as anti-cancer agents to exploit its potent angiostatic properties (NIH, 2007). However, clinical progress has been hindered by challenges including poor pharmacokinetic profiles and potential metabolic side effects related to CD36's role in lipid metabolism (Frontiers in Pharmacology, 2015).

Other names

CD36-TSP1 complexCD36-thrombospondin-1 axisCD36-TSR complexCD36-VEGFR2-beta1 integrin complexCD36-containing multi-protein signaling complex

Activation of the CD36-mediated anti-angiogenic pathway through recruitment of Src-family kinases (e.g., Fyn) and activation of p38 MAPK/JNK, or inhibition of VEGFR2 signaling via recruitment of the phosphatase SHP-1.