A p38α-selective chemosensor for use in unfractionated cell lysates

Cliff I. Stains, Elvedin Luković, Barbara Imperiali

Research output: Contribution to journalArticle

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Abstract

Recent efforts have identified the p38α Ser/Thr kinase as a potential target for the treatment of inflammatory diseases as well as non-small cell lung carcinoma. Despite the significance of p38α, no direct activity probe compatible with cell lysate analysis exists. Instead, proxies for kinase activation, such as phosphospecific antibodies, which do not distinguish between p38 isoforms, are often used. Our laboratory has recently developed a sulfonamido-oxine (Sox) fluorophore that undergoes a significant increase in fluorescence in response to phosphorylation at a proximal residue, allowing for real-time activity measurements. Herein we report the rational design of a p38α-selective chemosensor using this approach. We have validated the selectivity of this sensor using specific inhibitors and immunodepletions and show that p38α activity can be monitored in crude lysates from a variety of cell lines, allowing for the potential use of this sensor in both clinical and basic science research applications.

Original languageEnglish (US)
Pages (from-to)101-105
Number of pages5
JournalACS chemical biology
Volume6
Issue number1
DOIs
StatePublished - Jan 21 2011

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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