Novel Mammalian Putative Phosphatidylinositol-4-Phosphate-5-Kinase

Case ID:
98-431

This invention is a novel mammalian gene involved in membrane trafficking, more specifically, insulin‑induced translocation of the fat/muscle-specific glucose transporter GLUT4.

 

Background & Unmet Need:

Both Type I (Juvenile onset) and Type II (Maturity onset) Diabetes Mellitus result in a profound state of high glucose in the circulation.  This is caused either by a lack of insulin or a failure in the insulin‑regulated circuit that transfers glucose molecules from the blood into the cells, thereby causing blood glucose levels to decline.  Insulin’s action to stimulate glucose entry into the cell involves a dramatic increase of glucose transporter molecules, called GLUT4, which are found on the surface of fat and muscle cells.  These transporters are responsible for glucose influx.  Exactly how GLUT4 sorts, directs, and delivers insulin to the cell surface is currently unknown.  Our researchers rationalized that the insulin-signaling mechanism(s) and/or membrane trafficking machinery used by GLUT4 involves tissue‑specific molecular components.

 

Technology Description:

Using a PCR-based mRNA differential display screen for fat/muscle unique sequences in a mouse model, our researchers have isolated a cDNA fragment (363 base pairs) with an amino acid sequence closely related to a phosphatidylinositol‑4‑phosphate‑5‑kinase that is involved in yeast membrane trafficking and which generates PI 4,5‑bisphosphate (PI 4,5‑P2).  The biosynthesis of PI 4, 5-P2 has attracted increasing interest because of mounting evidence implicating metabolites of PI 4, 5-P2 as important regulators of many cellular processes.  In particular, PI 4, 5-P2 is a key substrate of insulin-activated enzymes that are important elements in insulin action of GLUT4 membrane movements. 

 

Commercial Applications:

  • Rational drug design targeting the new protein
  • Development of diagnostic tests for gene defects related to specific disease states
  • Development of gene delivery technology
  • Identification of other interacting proteins (receptors, etc.) that may be related to the gene’s function and overall insulin action

 

Stage of Development:

Preclinical

 

Competitive Advantages:

  • Provides a direct substrate target for drug manipulation of insulin activity

 

Intellectual Property Status:

Patent application filed

 

Related Publications or Citations of Work:

None

Patent Information:
For Information, Contact:
Joan Dunbar
Associate Vice President for Technology Commercialization
Wayne State University
(313) 577-5542
jcdunbar@med.wayne.edu
Inventors:
Assia Shisheva
Keywords:
DNA
Drug Target
Therapeutics