The recently cloned ATM gene is mutated in patients with ataxia telangiectasia, but its biological functions remain to be experimentally determined. Structural analysis has revealed ATM sequence similarities to the catalytic domains of phosphatidyl-3 kinase and other members of this family of yeast and mammalian proteins. Rabbit polyclonal antibodies raised against polypeptide regions unique to the COOH terminus and to the NH2 terminus of the published ATM sequence confirm ATM as Mr ∼350,000 protein in normal cells, which is missing in AT cells. Immunoprecipitated protein(s) is capable of phosphorylating IκB-α in an in vitro kinase assay. However, we did not observe a phosphatidyl-3 kinase or a DNA-dependent protein kinase function by ATM immunoprecipitates. These data support a protein kinase activity for ATM and suggest a role in NF-κB activation.


This work was supported in part by NIH Grants CA63023 (to M. J.) and CA45408 (to A. D.).

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