IDENTIFICATION OF CDC7 AS A NEW REGULATOR OF T CELL ACTIVATION

Abstract

In this thesis, a novel screening assay was designed to identify novel mediators of TCR signalling. A library of kinase inhibitors was screened for their effects on suppressing activation in several T cell populations. The screening assay was able to identify inhibitors of canonical kinases of TCR signalling and kinases that were not previously characterised in TCR signalling. Through the screening assay, a dual inhibitor of the kinases Cdc7 and Cdk9, PHA-767491, was identified to inhibit various markers of T cell activation. PHA-767491 has an inhibitory effect on the TCR signalling pathway as Erk phosphorylation was suppressed. Furthermore, the data indicate that Cdc7 activity is increased upon TCR stimulation. In summary, the results suggest that Cdc7 could be a novel mediator of the TCR signalling network.