Dynamic reprogramming of the kinome in response to MEK and other kinase inhibitors.

Lee M. Graves, The University of North Carolina, Chapel Hill, USA

The kinome is a highly integrated network of kinases whose activities are controlled by feedback phosphorylation, cross-talk and transcriptional modulation. We are using a kinome profiling technology based on kinase capture and quantification on immobilized kinase inhibitor beads. This technology known as multiplexed inhibitor beads (MIBs) coupled with quantitative mass spectrometry (MS) provides a unique approach to investigate kinase activity and expression changes in disease or in response to pharmacological treatments. We have applied MIBs/MS to profile kinome changes in response to MEK, IKK and other kinase inhibitors. Our research demonstrates that the kinome is dynamic and rapidly remodels in response to selective inhibition of specific kinase pathways. The results of these studies will be discussed.