The Neurotrophic and Antiangiogenic Functions of PEDF: A Reflection of its Variable Phosphorylation States

The pigment epithelium-derived factor (PEDF) is a non-inhibitory serpin, which is expressed mainly in the eye, but was also reported to be present in the adult human brain, spinal cord and plasma. It is characterized as a neurotrophic/ neuroprotective factor and one of the most potent natural inhibitors of angiogenesis in the eye, where it plays a physiological regulatory role in retinal angiogenesis. In this review we describe the expression, structure-function relationships, biological activities and regulation of PEDF. In addition, we emphasize our recent findings on the role of extracellular phosphorylation in PEDF activity, and show that the neurotrophic and antiangiogenic functions of PEDF are highly influenced by its phosphorylation state. Hence, phosphorylation of PEDF may be one of the modes that determine its specific physiological outcome.