ATM kinase compositions and methods
AssigneeSt. Jude Children's Research Hospital
InventorsMichael B. Kastan, Christopher Bakkenist
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Abstract
The present invention provides methods for detecting activation of ATM kinase, DNA damage, and DNA damaging agents. Further provided are antibodies which specifically recognize the phosphorylation state of Ataxia Telangiectasia-Mutated (ATM) kinase. Methods of identifying agents which modulate the activation and activity of ATM kinase are also provided.
Claims34
A method of identifying the activation state of Ataxia-Telangiectasia Mutated kinase in a cell comprising determining the phosphorylation state of a serine corresponding to residue 1981 of Ataxia-Telangiectasia Mutated kinase of SEQ ID NO:1 in a cell wherein the phosphorylation state of said serine is indicative of the activation state of Ataxia-Telangiectasia Mutated kinase.
An antibody specific for Ataxia-Telangiectasia Mutated kinase wherein the antibody specifically recognizes the phosphorylation state of a serine corresponding to residue 1981 of Ataxia-Telangiectasia Mutated kinase of SEQ ID NO:1.
A method of producing soluble Ataxia-Telangiectasia Mutated kinase or a fragment thereof comprising contacting a first polypeptide which contains the Ataxia-Telangiectasia Mutated kinase domain with a second polypeptide which contains a serine residue 1981 of Ataxia-Telangiectasia Mutated kinase of SEQ ID NO:1 so that soluble Ataxia-Telangiectasia Mutated kinase is produced.
A method of enhancing a cellular response to DNA damage comprising administering an effective amount of an agent which agonizes the activation of Ataxia-Telangiectasia Mutated kinase so that a cellular response to DNA damage is enhanced.
A method of identifying an agent that inhibits Ataxia-Telangiectasia Mutated kinase activity comprising contacting soluble Ataxia-Telangiectasia Mutated kinase protein with an agent and a phosphate donor and determining the phosphorylation state of a serine of said soluble Ataxia-Telangiectasia Mutated kinase corresponding to residue 1981 of Ataxia-Telangiectasia Mutated kinase of SEQ ID NO:1 wherein the phosphorylation state of said serine is indicative of said kinase activity.
Dependencies are inferred from the claim text.