Abstract: The present invention relates to identification of the consensus sequence phosphorylated by ATM kinase. This, in turn, permitted identification of ATM kinase target proteins, and development of a convenient assay system for ATM kinase phosphorylation using fusion polypeptides as substrates. The assay system is adaptable to screening for ATM modulators, particularly inhibitors. In a specific embodiment, the substrate recognition sequence and mutagenized variants of this sequence were incorporated in a GST fusion protein and assayed for phosphorylation by ATM kinase. This assay system is useful in screening for ATM inhibitors. ATM function assays were validated using an ATM-kinase dead dominant-negative mutant.
Type:
Grant
Filed:
September 21, 1999
Date of Patent:
February 19, 2002
Assignees:
St. Jude Childre's Research Hospital, Johns-Hopkins University
Inventors:
Michael Kastan, Christine Canman, Seong-Tae Kim, Dae-Sik Lim