Vascular endothelial growth factor receptor 2 signaling complex via CD36 and beta-1 integrin (VEGFR2-CD36-ITGB1 complex)

The Vascular endothelial growth factor receptor 2 (VEGFR2) signaling complex via CD36 and beta-1 integrin is a multi-protein assembly essential for the regulation of angiogenesis in endothelial cells (UniProt: P35968, P16671, P05556). This complex acts as a molecular switch where the scavenger receptor CD36 and beta-1 integrins (ITGB1) interact with VEGFR2 to modulate its responsiveness to vascular endothelial growth factor (VEGF). Under physiological conditions, the binding of endogenous inhibitors like Thrombospondin-1 (TSP-1) to CD36 promotes the association of CD36 and beta-1 integrins with VEGFR2, leading to the recruitment of phosphatases that dephosphorylate VEGFR2 and suppress its pro-angiogenic activity (Chu et al., 2013, Blood). In pathological states such as cancer, this inhibitory complex is often disrupted, allowing for uncontrolled vessel growth and tumor progression. Therapeutic interventions targeting this complex include monoclonal antibodies against VEGFR2, such as Ramucirumab, and TSP-1 mimetics like ABT-510 that aim to restore the inhibitory signaling (Zhang et al., 2015, Blood). This complex is also a significant factor in the development of resistance to anti-VEGF therapies, making it a high-interest target for combination treatments in oncology and ophthalmology.

Other names

CD36-VEGFR2-ITGB1 complexTSP1-CD36-VEGFR2 inhibitory complexVEGFR2-CD36-Integrin beta-1 axis

The complex functions by recruiting CD36 and beta-1 integrins to VEGFR2 upon ligand binding (e.g., Thrombospondin-1), which facilitates the recruitment of phosphatases like SHP-1 to dephosphorylate and inhibit VEGFR2 signaling (Chu et al., 2013, Blood; Zhang et al., 2015, Blood).