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. Author manuscript; available in PMC: 2008 Jun 16.
Published in final edited form as: J Biol Chem. 2007 Apr 5;282(21):15404–15415. doi: 10.1074/jbc.M701638200

Fig. 9. Model for CD36-dependent activities of TSP1 and other CD36 ligands.

Fig. 9

Uptake of myristic acid via the fatty acid translocase (FAT) activity of CD36 is potently inhibited by the TSP1-derived mimetic p907 and by the angiogenesis-inhibiting CD36 antibody SMΦ (10). TSP1 inhibits FAT activity, and CD36 antibody FA6-152 is known to antagonize the anti-angiogenic activity of TSP1 (10,12,13) but does not itself inhibit FAT. In serum starved endothelial cells, inhibiting myristic acid transport is proposed to limit precursor for synthesis of myristoyl-CoA via the acyl-CoA synthase (ACSL3), which is then transferred by N-myristoyl transferases (NMT) to proteins bearing subterminal Gly residues exposed by Met aminopeptidases (MetAP). Of these, MetAP2 is the known target of several angiogenesis inhibitors (58), suggesting convergence of the signaling pathways induced by these inhibitors and TSP1. Limiting myristoylation prevents translocation of Fyn and other myristoylated proteins to membranes and indirectly limits eNOS activity. TSP1 at 1–10 nM limits cGMP signaling by inhibiting myristate uptake via CD36 and at 10–100 pM also inhibits sGC activation via CD47 (22).