Pigment epithelium-derived factor receptor (PEDF-R): a plasma membrane-linked phospholipase with PEDF binding affinity.
Pigment epithelium-derived factor (PEDF), a multifunctional protein, acts in retinal differentiation, survival and maintenance by interacting with high affinity receptors on the surface of target cells. We have recently identified PEDF-R, a new member of the patatin-like phospholipase domain-containing 2 (PNPLA2) family with characteristics of a PEDF receptor. The PEDF-R sequence reveals a patatin-like phospholipase domain toward its amino-end, and four transmembrane domains interrupted by two extracellular loops and three intracellular regions along its polypeptide sequence. This newly identified protein is present on the surface of retina and RPE cells, and has the expected transmembrane topology. It has specific and high binding affinity for PEDF, and exhibits a potent phospholipase A(2) activity that liberates fatty acids. Most importantly, PEDF binding stimulates the enzymatic phospholipase A(2) activity of PEDF-R. In summary, PEDF-R is a novel component of the retina that is a phospholipase-linked membrane protein with high affinity for PEDF. The results suggest a molecular pathway by which PEDF ligand/receptor interactions on the cell surface could generate a cellular signal. These conclusions enhance our understanding of the role of PEDF as a neurotrophic survival factor.
NEI-NIH, Bethesda, MD 20892-0608, USA.
Preeti
P
Subramanian
Patricia M
PM
Notario
S Patricia
SP
Becerra
D002462:Cell Membrane / Q000201:enzymology*; D019295:Computational Biology; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009414:Nerve Growth Factors / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D018013:Receptors, Neuropeptide / Q000737:chemistry / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000201:enzymology; D015843:Serpins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D008024:Ligands; D009414:Nerve Growth Factors; D010740:Phospholipases; D018013:Receptors, Neuropeptide; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C400531:pigment epithelium-derived factor receptor