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ATM Gene Product Phosphorylates IB-¹

Division of Radiation Research, Departments of Radiation Medicine and Microbiology, Vincent T. Lombardi Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007

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 M_r 350,000 protein in normal cells, which is missing in AT cells. Immunoprecipitated protein(s) is capable of phosphorylating IB- 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-B activation.

¹ This work was supported in part by NIH Grants CA63023 (to M. J.) and CA45408 (to A. D.).

² To whom requests for reprints should be addressed, at Department of Radiation Medicine, Division of Radiation Research, The Research Building, E211A, Washington, DC 20007. Phone: (202) 687-8352; Fax: (202) 687-0400.

Received 9/ 6/96. Accepted 11/ 8/96.

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