Systematic analysis of the interacting proteins of Aurora-A protein kinase by protein array

• Main Authors: Yu-Wen Liu, 劉育妏
• Other Authors: Chi-Ying F. Huang
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/50157159895441386682

碩士 === 國立陽明大學 === 生物藥學研究所 === 96 === Aurora-A is a mitotic serine-threonine kinase and orchestrates key aspects of cell division. Aurora-A has drawn lots of attention recently because overexpression of this protein kinase has been found in various epithelial malignant tumors, such as breast and lung, due to either gene amplification, transcriptional deregulation or defect in protein stability and kinase activity. To systematically reveal the role of Aurora-A, we employ protein array (ProtoArrayTM), containing ~5000 baculovirus expressed proteins, to accelerate the identification of the interacting proteins of Aurora-A. Of 42 newly identified interacting proteins, six novel proteins, including EGFR, were further confirmed to associate with Aurora-A. In fact, both Aurora-A and EGFR are overexpressed in advanced non-small cell lung cancer (NSCLC). Furthermore, it is often seen mutations within kinase domain of EGFR in NSCLC, especially in Asia. Interestingly, Aurora-A has preference association with EGFR-mutants (i.e. L858R). The C-terminal tyrosine kinase domain of EGFR was mapped to interact with Aurora-A. Moreover, EGFR mutant colocalized, at least in part, with Aurora-A at spindle pole in mitosis. Together, application of ProtoArrayTM in searching for interacting partners of Aurora-A may provide novel mechanistic insights toward this potential drug target.