Human Biliverdin Reductase is a New Member of the Insulin Receptor Substrate Family with Serine/Threonine/Tyrosine Kinase Activity

Applications:
Human biliverdin reductase (BVR) is an evolutionary conserved soluble enzyme that was originally characterized in the context of its reductase activity (conversion of biliverdin to bilirubin) and more recently shown to possess serine/threonine/tyrosine kinase activity.  The present work demonstrates that this dual kinase activity of BVR may play a role in the insulin signaling pathway. First, BVR acts as a substrate for insulin receptor (IR) tyrosine kinase activity and subsequent activation of BVR is thought to block insulin mediated glucose uptake.  In addition, BVR acts as a kinase for insulin receptor substrate protein-1 (IRS-1) serine phosphorylation.  Serine phosphorylation of IRS-1 is also inhibitory to insulin signaling and insulin mediated glucose uptake.  The antagonistic action of BVR on insulin signaling was further demonstrated in siRNA studies in which an increase in glucose uptake in response to insulin was observed when expression of BVR was “knocked-down.”

Advantage
The invention identifies a potentially new target for treatment of diabetes, etc.

URV Reference Number: 6-1384
Patent Information:
Category(s):
Therapeutic
For Information, Contact:
Blaze Pharoah
Licensing Manager
University of Rochester
585-276-6600
blaze_pharoah@urmc.rochester.edu
Inventors:
Mahin Maines
Keywords:
Cell Signalling
Therapy