FIGURE 8.

Scheme to illustrate our current understanding of PEDF·PEDF-R interactions. Plasma membranes of retina cells contain transmembrane PEDF-R, which is essential for PEDF-mediated survival and antiapoptotic effects. The amino acids Ser⁴⁷ and Asp¹⁶⁶ of PEDF-R are critical for lipase activity. PEDF binds to the LBD within the L4 ectodomain of PEDF-R to stimulate PLA₂ activity. Left, it is proposed that the PLA₂ activity would lead to the release of fatty acids and lysophospholipids from phospholipid substrates present in the lipid bilayer of plasma membranes. The products activate yet unknown signaling pathways to up-regulate Bcl-2 and cell survival (solid lines). Right, LBD-containing peptides (e.g. E5b and P1) act as soluble receptors that bind free PEDF to compete with binding to LBD, resulting in blocking of the survival activity of PEDF (dotted lines). ×, blocking.