Document Detail


Expanding applications of chemical genetics in signal transduction.
MedLine Citation:
PMID:  22544320     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chemical genetics represents an expanding collection of techniques applied to a variety of signaling processes. These techniques use a combination of chemical reporters and protein engineering to identify targets of a signaling enzyme in a global and non-directed manner without resorting to hypothesis-driven candidate approaches. In the last year, chemical genetics has been applied to a variety of kinases, revealing a much broader spectrum of substrates than had been appreciated. Here, we discuss recent developments in chemical genetics, including insights from our own proteomic screen for substrates of the kinase ERK2. These studies have revealed that many kinases have overlapping substrate specificity, and they often target several proteins in any particular downstream pathway. It remains to be determined whether this configuration exists to provide redundant control, or whether each target contributes a fraction of the total regulatory effect. From a general perspective, chemical genetics is applicable in principle to a broad range of posttranslational modifications (PTMs), most notably methylation and acetylation, although many challenges remain in implementing this approach. Recent developments in chemical reporters and protein engineering suggest that chemical genetics will soon be a powerful tool for mapping signal transduction through these and other PTMs.
Authors:
Scott M Carlson; Forest M White
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-05-15
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  11     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-09-24     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1903-9     Citation Subset:  IM    
Affiliation:
Department of Biological Engineering; Massachusetts Institute of Technology; Cambridge, MA, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylation
HeLa Cells
Humans
Methylation
Mitogen-Activated Protein Kinase 1 / genetics,  metabolism
Pharmacogenetics*
Phosphorylation
Protein Engineering
Protein Processing, Post-Translational
Proteins / genetics,  metabolism*
Proteomics
Signal Transduction*
Substrate Specificity
Grant Support
ID/Acronym/Agency:
5P30CA014051/CA/NCI NIH HHS; R01CA118705/CA/NCI NIH HHS; R01DK42816/DK/NIDDK NIH HHS; U54CA112967/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Proteins; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1
Comments/Corrections

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