Identification and Isolation of the Receptor for Pigment Epithelium-derived Factor (PEDF)
Description of Invention:
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.
Applications:
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 http://www.nei.nih.gov/intramural/protein_struct_func.asp. 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:
S. Patricia Becerra (NEI) Luigi Notari (NEI) Jorge Laborda (CDER/FDA) et al.
Patent Status:
DHHS Reference No. E-314-2003/0 --
U.S. Provisional Application No. 60/493,713 filed 07 Aug 2003, now abandoned
DHHS Reference No. E-314-2003/1 --
U.S. Provisional Application No. 60/579,177 filed 12 Jun 2004, now abandoned
DHHS Reference No. E-314-2003/2 --
PCT/US2004/025560 filed 05 Aug 2004, which published as WO 2005/014645 A2 on 17 Feb 2005, now expired
U.S. Patent Application No. 10/566,540 filed 16 Oct 2006, entitled "PEDF-R Receptor and Uses," is pending. The U.S. Application has not been published. Only U.S. Patent protection has been sought for this technology. There are no foreign counterpart patent applications.
Relevant Publication:
The patent application has been published as WO 2005/014645 A2 on 17 Feb 2005.
L Notari et al. Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. J Biol Chem. 2006 Dec 8; 281(49):38022-38037. [PubMed abs]
Licensing Status: This application is available for license on a non-exclusive or exclusive basis.
Biological Materials Availability:
Biological materials related to this technology are not available at this time.
Portfolios: Ophthalmology Central Nervous System Cancer
Cancer -Therapeutics Central Nervous System -Therapeutics-neurological Ophthalmology -Therapeutics-biological
For Additional Information Please Contact: Susan S. Rucker J.D.
NIH Office of Technology Transfer
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Phone: (301) 435-4478
Email: ruckersu@mail.nih.gov
Fax: (301) 402-0220
