A chemical switch for inhibitor-sensitive alleles of any protein kinase View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-09

AUTHORS

Anthony C. Bishop, Jeffrey A. Ubersax, Dejah T. Petsch, Dina P. Matheos, Nathanael S. Gray, Justin Blethrow, Eiji Shimizu, Joe Z. Tsien, Peter G. Schultz, Mark D. Rose, John L. Wood, David O. Morgan, Kevan M. Shokat

ABSTRACT

Protein kinases have proved to be largely resistant to the design of highly specific inhibitors, even with the aid of combinatorial chemistry. The lack of these reagents has complicated efforts to assign specific signalling roles to individual kinases. Here we describe a chemical genetic strategy for sensitizing protein kinases to cell-permeable molecules that do not inhibit wild-type kinases. From two inhibitor scaffolds, we have identified potent and selective inhibitors for sensitized kinases from five distinct subfamilies. Tyrosine and serine/threonine kinases are equally amenable to this approach. We have analysed a budding yeast strain carrying an inhibitor-sensitive form of the cyclin-dependent kinase Cdc28 (CDK1) in place of the wild-type protein. Specific inhibition of Cdc28 in vivo caused a pre-mitotic cell-cycle arrest that is distinct from the G1 arrest typically observed in temperature-sensitive cdc28 mutants. The mutation that confers inhibitor-sensitivity is easily identifiable from primary sequence alignments. Thus, this approach can be used to systematically generate conditional alleles of protein kinases, allowing for rapid functional characterization of members of this important gene family. More... »

PAGES

395

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/35030148

DOI

http://dx.doi.org/10.1038/35030148

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1007129994

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11014197


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

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N-Triples is a line-based linked data format ideal for batch operations.

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Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/35030148'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/35030148'


 

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