Spring 2010 Events

February 11, 2010
Dr. Sanjay Kumar , Queens College
Towards Acquisition of Activity-Based Biosensors and Small Molecule Inhibitors of Nek2 - A Kinase Implicated In Cancer
A direct activity-based measurement of a kinase in a natural intracellular environment is crucial for correlating activity with its in-vivo function. To date, majority of the traditional biochemical methods used to monitor intracellular kinase activity employ indirect approaches. This process typically involves cell lysis and affinity purification of target kinase at a predetermined time interval, followed by kinase activity measurements using radioactivity (e.g. ³²P and ³³P). Such indirect and discontinuous measurement of kinase activity is often not sufficient for making intracellular functional assignments, because it is known that a complex cellular microenvironment can have a dramatic impact on kinase activity.

Nek2 is a centrosomal serine/threonine kinase and its expression is significantly elevated in many different forms of cancer. Despite its involvement in a variety of cancer types, many of its precise intracellular roles in oncogenic transformation remain to be discovered (e.g. how over-expression of Nek2 leads to tumor formation and progression, and, if over-expression is indeed correlated with aberrant activity of Nek2, leading to uncontrolled cell proliferation). This gap in our understanding of Nek2 biology is primarily due to the lack of available chemical tools needed for in-vivo applications. Furthermore, it needs to be established if small molecule inhibition of intracellular Nek2 kinase activity is a promising strategy for cancer drug development. Currently there are no potent and specific inhibitory agents of Nek2 kinase. We are developing activity-based, fluorescence-responsive specific biosensors, and small molecule inhibitory agents of Nek2 kinase that will be used to delineate the undocumented function of this kinase in both normal and diseased cancer cells.