Molecules 2012, 17(10), 12172-12186; doi:10.3390/molecules171012172
Review

The Final Link: Tapping the Power of Chemical Genetics to Connect the Molecular and Biologic Functions of Mitotic Protein Kinases

1 Graduate Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI 53705, USA 2 Department of Medicine and UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53705, USA
* Author to whom correspondence should be addressed.
Received: 17 September 2012; in revised form: 26 September 2012 / Accepted: 12 October 2012 / Published: 17 October 2012
(This article belongs to the Special Issue Chemical Genetics)
PDF Full-text Download PDF Full-Text [443 KB, uploaded 17 October 2012 10:30 CEST]
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 rapid and specific interrogation of kinase function. Moreover, combining these tools with advanced proteomics and substrate labeling has identified phosphorylation sites on numerous protein targets. Here, we review the chemical genetic tools available to study kinase function and identify substrates. We describe how chemical genetics can also be used to link kinase function with cognate phosphorylation events to provide mechanistic detail. This can be accomplished by dissecting subsets of kinase functions and chemical genetic complementation. We believe a complete “chemical genetic toolbox” will ultimately allow a comprehensive understanding of how protein kinases regulate mitosis.
Keywords: chemical biology; protein kinases; separation of function; mitosis; cell division

Article Statistics

Load and display the download statistics.

Citations to this Article

Cite This Article

MDPI and ACS Style

Lera, R.F.; Burkard, M.E. The Final Link: Tapping the Power of Chemical Genetics to Connect the Molecular and Biologic Functions of Mitotic Protein Kinases. Molecules 2012, 17, 12172-12186.

AMA Style

Lera RF, Burkard ME. The Final Link: Tapping the Power of Chemical Genetics to Connect the Molecular and Biologic Functions of Mitotic Protein Kinases. Molecules. 2012; 17(10):12172-12186.

Chicago/Turabian Style

Lera, Robert F.; Burkard, Mark E. 2012. "The Final Link: Tapping the Power of Chemical Genetics to Connect the Molecular and Biologic Functions of Mitotic Protein Kinases." Molecules 17, no. 10: 12172-12186.

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert