Download Facile Kinase Activation with Membrane Permeable Small

Research Reagents/Methodology/Tools
Facile Kinase Activation with Membrane Permeable Small
Molecules
Researchers at UNC have developed a simple method of activating and deactivating
protein kinases via membrane permeable small molecules. This has been
accomplished by modifying the kinase domain with an engineered small protein
domain that can be inserted into any kinase at a highly conserved position. Insertion
of the domain turns off the kinase active site but does not affect other interactions,
providing the kinetic control of inhibitors with the absolute specificity of
genetics. The kinase is activated when specific small molecules are added to the
medium. To date this has been accomplished with rapamycin, non-immunogenic
rapamycin analogs, and other small molecules. The method allows for precise
control of activation kinetics, has been validated in living cells, and is undergoing
validation in mice.
Benefits
- Technology can be used for high content screening of protein activity
- Broadly applicable – data indicates ready application to many kinases
- Fully genetically encoded - useful for in vitro screening
- Allows for examination of the effect of protein activity on specific
organs and tumors
- Can be used for research studies of protein dynamics and to target
protein expression under drug control
The Technology
Proteins are an essential part of many biological processes. In order to
screen protein activity in living cells or to study protein function, it is
valuable to have the capacity to turn proteins “on” or “off”. This can be
done via genetic manipulation. However, genetic manipulation is slow
and can lead to compensatory mechanisms within the cell that alter
protein function. Small molecules have much faster effects than genetic
manipulation, but suffer from lack of specificity and are not available
for many targets. Therefore, a technique that allows for activation of
protein kinases in a relatively simple, rapid and specific manner would
be ideal.
For More Information
If you would like more
information about this technology
or UNC - Chapel Hill's technology
transfer program, please contact:
Office of Technology
Development
Phone:
Fax:
Email:
http://research.unc.edu/otd/
Office of Technology
Development
UNC - Chapel Hill
100 Europa Drive, Suite 430
Chapel Hill, NC 27517
Ref: 08-0098
02.12.15
Dr. Klaus Hahn and colleagues at UNC Chapel Hill have developed a
relatively simple method that can be used to activate protein
kinases. The method employs a membrane permeable drug which can be
added to a cell medium to activate protein kinases. Proof of concept has
been demonstrated for the focal adhesion kinase (FAK), Src, p38, yes,
fyn, pak and lyn. The discovery also provides a means for precise
control of activation kinetics. The technology has been applied to both
serine/threonine and tyrosine kinases.
Opportunity
UNC's Office of Technology Development seeks to stimulate
development and commercial use of UNC-developed technologies.
UNC is flexible in its agreements, and opportunities exist for joint
development, academic or commercial licensing (exclusive,
non-exclusive, and field-of-use), publishing, or other mutually beneficial
relationships. UNC is pursuing U.S. and international intellectual
property protection for this innovation.