Journal article
The Final Link: Tapping the Power of Chemical Genetics to Connect the Molecular and Biologic Functions of Mitotic Protein Kinases
Molecules (Basel, Switzerland), Vol.17(10), pp.12172-12186
10/17/2012
DOI: 10.3390/molecules171012172
PMCID: PMC3620603
PMID: 23075814
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.
Details
- Title: Subtitle
- The Final Link: Tapping the Power of Chemical Genetics to Connect the Molecular and Biologic Functions of Mitotic Protein Kinases
- Creators
- Robert F. Lera - Univ Wisconsin, Grad Program Cellular & Mol Biol, Madison, WI 53705 USAMark E. Burkard - Univ Wisconsin, Dept Med, Madison, WI 53705 USA
- Resource Type
- Journal article
- Publication Details
- Molecules (Basel, Switzerland), Vol.17(10), pp.12172-12186
- DOI
- 10.3390/molecules171012172
- PMID
- 23075814
- PMCID
- PMC3620603
- NLM abbreviation
- Molecules
- ISSN
- 1420-3049
- eISSN
- 1420-3049
- Publisher
- Mdpi
- Number of pages
- 15
- Grant note
- 9U54TR000021 / NIH CTSA of the NCATS R01GM097245 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) UL1TR000427 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) 062541_YCSA / Flight Attendant Medical Research Institute R01 GM097245 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 10/17/2012
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984701257302771
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