Chemical Rescue of a Mutant Enzyme in Living Cells

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

Science, Vol. 311, No. 5765. (3 March 2006), pp. 1293-1297.

View FullText article

DOI, HighWire, Pubmed, Hubmed

Reviews [Write a review of this article]

There are no reviews of this article

Find related articles from these CiteULike users

Yanno, dchughes, G4ID (group), Genetics-of-Gambling (group)

Find related articles with these CiteULike tags

cancer, chemical, chemical-rescue, drugdiscovery, modeofaction, oncogene, src

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.

@article{citeulike:528044, 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.}, author = {Qiao, Yingfeng and Molina, Henrik and Pandey, Akhilesh and Zhang, Jin and Cole, Philip A. }, citeulike-article-id = {528044}, doi = {http://dx.doi.org/10.1126/science.1122224}, journal = {Science}, keywords = {chemical, drugdiscovery, modeofaction}, month = {March}, number = {5765}, pages = {1293--1297}, posted-at = {2006-03-03 13:18:46}, priority = {0}, title = {Chemical Rescue of a Mutant Enzyme in Living Cells}, url = {http://dx.doi.org/10.1126/science.1122224}, volume = {311}, year = {2006} }

RIS record

TY - JOUR ID - citeulike:528044 L3 - citeulike-article-id:528044 N2 - 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. IS - 5765 JF - Science EP - 1297 TI - Chemical Rescue of a Mutant Enzyme in Living Cells VL - 311 SP - 1293 KW - chemical KW - drugdiscovery KW - modeofaction AU - Qiao, Yingfeng AU - Molina, Henrik AU - Pandey, Akhilesh AU - Zhang, Jin AU - Cole, Philip PY - 2006/03/03/ UR - http://dx.doi.org/10.1126/science.1122224 ER -

RIS BibTeX