Identification and Isolation of the Receptor for Pigment Epithelium-derived Factor (PEDF)


This application describes and claims compositions and methods related to PEDF-R, a receptor for pigment epithelium-derived factor (PEDF). PEDF (aka serpin f1 gene product) is a protein, belonging to the serpin superfamily with neurotrophic, gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. However, PEDF lacks the characteristic ability of serpins to inhibit serine protease activity. In particular, the compositions and methods described and claimed in this application are related to the isolation, cloning, expression and characterization of a receptor for PEDF, PEDF-R. The PEDF-R gene (also known as TTS-2.2, iPLA-zeta, ATGL, desnutrin, or PNPLA2) is located on chromosome 11. The sequence of the PEDF-R polypeptide is composed of 504 amino acids, and shares homology with other genes such as for adiponutrin and GS2, contains a patatin-like phospholipase A2 domain and up to four transmembrane regions. PEDF-R exhibits a potent phospholipase A2 activity, binds to PEDF ligands with high affinity, and it localizes to plasma membranes. An extracellular loop region is available for the interactions with extracellular PEDF ligand, which stimulate the phospholipase activity of PEDF-R. The identification of this novel PEDF-R gene in the retina for a phospholipase-linked membrane protein with high affinity for PEDF, suggests a molecular pathway by which ligand/receptor interaction on the cell surface could generate a cellular signal.



Potential Commercial Applications: Competitive Advantages:
  • Basic research to further elucidate the role of PEDF and its receptor in signal transduction pathways.
  • Development of drug screening assays to identify agonists and antagonists of PEDF activity.
  • Development of new biological molecules to regulate PEDF signaling such as monoclonal antibodies and chimeric IgG-receptor constructs.
 


Development Stage:

Information on research being conducted in Dr. Becerra’s laboratory can be found on the internet at https://irp.nih.gov/pi/s-patricia-becerra. The ability of the receptor or receptor-targeted molecules and biologics to be used as therapeutics remains the subject of early research and development efforts.



Inventors:

Luigi Notari (NEI)  ➽ more inventions...

Jorge Laborda (FDA)  ➽ more inventions...


Intellectual Property:
US Application No. 60/493,713
US Application No. 60/579,177
US Application No. 10/566,540
PCT Application No. PCT/US2004/25560

Publications:

The patent application has been published as WO 2005/014645 A2 on 17 Feb 2005.

PMID 17032652

Notari L, et al.



Licensing Contact:
Edward (Tedd) Fenn, J.D.
Email: tedd.fenn@nih.gov
Phone: 240-276-6833

OTT Reference No: E-314-2003-0
Updated: May 7, 2018