Chemical rescue of a mutant enzyme in living cells

Yingfeng Qiao, Henrik Molina, Akhilesh Pandey, Jin Zhang, Philip A. Cole

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

The restoration of catalytic activity to mutant enzymes by small molecules is well established for in vitro systems. Here, we show that the protein tyrosine kinase Src arginine-388→alanine (R388A) mutant can be rescued in live cells with the use of the small molecule imidazole. Cellular rescue of a viral Src homolog was rapid and reversible and conferred predicted oncogenic properties. Using chemical rescue in combination with mass spectrometry, we confirmed six known Src kinase, substrates and identified several new protein targets. Chemical rescue data suggest that cellular Src is active under basal conditions. Rescue of R388A cellular Src provided insights into the mitogen-activated protein kinase pathway. This chemical rescue approach will likely have many applications in cell signaling.

Original languageEnglish (US)
Pages (from-to)1293-1297
Number of pages5
JournalScience
Volume311
Issue number5765
DOIs
StatePublished - Mar 3 2006

ASJC Scopus subject areas

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    Qiao, Y., Molina, H., Pandey, A., Zhang, J., & Cole, P. A. (2006). Chemical rescue of a mutant enzyme in living cells. Science, 311(5765), 1293-1297. https://doi.org/10.1126/science.1122224