The cellular form of the Abelson leukemia tyrosine kinase, cAbl, interacts with a variety of proteins, including cell-cycle regulators, and transcription factor and signaling adaptor proteins. A tight regulation of kinase activity is critical as aberrant activation of cAbl by oncogenic fusion with the breakpoint-cluster region (Bcr-Abl) has been identified as a driving mutation of chronic myelogenous leukemia and acute lymphocytic leukemia.
Although the conformational dynamics of the cAbl kinase was suggested to play a crucial role for its function, the regulatory mechanism of interconversion dynamics between different conformations is not understood. Regulatory domains of the cAbl kinase control the activity of kinase catalytic domain via allosteric fashion.
Our major interest is to understand the molecular mechanism by which the interdomain interfaces between the regulatory domains and the catalytic domain are controlled.