the final link tapping the power of chemical genetics to connect the molecular and biologic functions of mitotic protein kinases最后的链接挖掘化学遗传学的力量连接的分子和生物功能有丝分裂蛋白激酶.pdf

Molecules 2012, 17, 12172-12186; doi:10.3390/molecules171012172 OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review The Final Link: Tapping the Power of Chemical Genetics to Connect the Molecular and Biologic Functions of Mitotic Protein Kinases Robert F. Lera 1 and Mark E. Burkard 2,* 1 Graduate Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI 53705, USA; E-Mail: lera@ 2 Department of Medicine and UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53705, USA * Author to whom correspondence should be addressed; E-Mail: mburkard@; Tel.: +1-608-262-2803; Fax: +1-608-265-6905. Received: 17 September 2012; in revised form: 26 September 2012 / Accepted: 12 October 2012 / Published: 17 October 2012 Abstract: During mitosis, protein kinases coordinate cellular reorganization and chromosome segregation to ensure accurate distribution of genetic information into daughter cells. Multiple protein kinases contribute to mitotic regulation, modulating molecular signaling more rapidly than possible with gene expression. However, a comprehensive understanding of how kinases regulate mitotic progression remains elusive. The challenge arises from multiple functions and substrates, a large number of “bystander” phosphorylation events, and the brief window in which all mitotic events transpire. Analog-sensitive alleles of protein kinases are powerful chemical genetic tools for