| Activity-based probes for protein tyrosine phosphatases. | |
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MedLine Citation:
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PMID: 15148367 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Protein tyrosine phosphatases (PTPs) are involved in the regulation of many aspects of cellular activity including proliferation, differentiation, metabolism, migration, and survival. Given the large number and complexity of PTPs in cell signaling, new strategies are needed for the integrated analysis of PTPs in the whole proteome. Unfortunately, the activities of many PTPs are tightly regulated by posttranslational mechanisms, limiting the utility of standard genomics and proteomics methods for functional characterization of these enzymes. To facilitate the global analysis of PTPs, we designed and synthesized two activity-based probes that consist of alpha-bromobenzylphosphonate as a PTP-specific trapping device and a linker that connects the trapping device with a biotin tag for visualization and purification. We showed that these probes are active site-directed irreversible inactivators of PTPs and form a covalent adduct with PTPs involving the active site Cys residue. Additionally, we demonstrated that the probes are extremely specific toward PTPs while remaining inert to other proteins, including the whole proteome from Escherichia coli. Consequently, these activity-based PTP probes can be used to profile PTP activity in complex proteomes. The ability to interrogate the entire PTP family on the basis of changes in their activity should greatly accelerate both the assignment of PTP function and the identification of potential therapeutic targets. |
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Authors:
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Sanjai Kumar; Bo Zhou; Fubo Liang; Wei-Qing Wang; Zhonghui Huang; Zhong-Yin Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2004-05-17 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 101 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-05-26 Completed Date: 2004-07-09 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 7943-8 Citation Subset: IM |
Affiliation:
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Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Biotinylation Escherichia coli / enzymology*, genetics Molecular Probes / chemistry*, metabolism* Molecular Structure Protein Tyrosine Phosphatases / antagonists & inhibitors, chemistry, metabolism* Proteome / genetics, metabolism Proteomics Sensitivity and Specificity Substrate Specificity |
| Grant Support | |
ID/Acronym/Agency:
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1U54 AI057158/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Molecular Probes; 0/Proteome; EC 3.1.3.48/Protein Tyrosine Phosphatases |
| Comments/Corrections | |
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