PMC

CD36 wears multiple hats. As this review demonstrates functions of CD36 are homeostatic and contribute to normal cellular responses (CD36: The Good). However, in certain contexts, functions of CD36 contribute to pathological states (CD36: The Bad).
Uptake of apoptotic cells that occur as a part of normal homeostasis and in the context of inflammatory resolution
Uptake of pathogens; triggering the immune response
Uptake of modified proteins / lipids / lipoproteins that occur non-pathologically
Uptake of fatty acids
Inhibition of angiogenesis in the context of wound resolution
Down modulation of the immune response in the context of inflammatory resolution
Uptake of modified proteins / lipids / lipoproteins that occur in a pathological setting (e.g. hyperlipidemia, atherosclerosis, diabetes, alzheimer's disease)
Inhibition of angiogenesis in hyperlipidemic and diabetic settings
Triggering a pro-inflammatory response in the context of uptake of modified lipoprotein and protein ligands (e.g. fibrillar β-amyloid)
Dysregulation of insulin responsiveness as a result of fatty acid uptake in a diabetic setting

Binding of ligands to CD36 leads to cell specific activation of signaling pathways and responses. (A) Binding of TSR containing ligands of CD36, such as thrombospondin-1, leads to a specific signaling cascade involving the src kinase fyn, caspases and p38 MAP kinase in endothelial cells. The outcome of this pathway is apoptosis of the endothelial cell and inhibition of angiogenesis. (B) Binding of fibrillar β-amyloid to CD36 in a complex with other proteins (including SRA, CD47 and the integrin α₆β₁) on microglial cells can lead to activation of several pathways. The outcome of these signaling cascades is an “activated” state as a result of reorganization of the actin cytoskeleton to confer phagocytic competency, secretion of ROS and cytokines. (C) On the macrophage, binding of modified LDL to CD36 leads to activation of the src kinase lyn, downstream activation of the MAP kinase kinase, MEKK2, and ultimately jnk phosphorylation, which is essential to modified LDL uptake and foam cell formation.