FIGURE 1.

Knowledge gaps in CD36 and ERK5-mediated platelet prothrombotic signaling. Circulating oxidized lipids are recognized by platelet scavenger receptor CD36. Src family kinases, particularly Fyn and Lyn, associate with CD36 upon ligand recognition and promote downstream signaling events, including generation of reactive oxygen species superoxide anion and hydrogen peroxide from NADPH oxidase. Hydrogen peroxide in turn activates the redox-sensitive MAP kinase ERK5 through a yet to be defined mechanism. ERK5 links CD36 to a prothrombotic platelet phenotype by activating integrin αIIbβ3 for platelet aggregation and promoting caspase-dependent procoagulant phosphatidylserine externalization. The mechanisms of ERK5-mediated caspase activation are unclear. Furthermore, CD36 participates in signaling crosstalk with the collagen receptor GPVI to amplify phosphatidylserine externalization. The signaling crosstalk mechanisms are not clear and may involve specific family members of Src kinases. CD36, CD36.