ATM GENE-PRODUCT PHOSPHORYLATES I-KAPPA-B-ALPHA

The recently clone ATM gene is mutated in patients with ataxia telangi ectasia, but its biological functions remain to be experimentally dete rmined. Structural analysis has revealed ATM sequence similarities to the catalytic domains of phosphatidyl-3 kinase and other members of th is family of yeast and mammalian proteins. Rabbit polyclonal antibodie s raised against polypeptide regions unique to the COOH terminus and t o the NH2 terminus of the published ATM sequence confirm ATM as M(r) s imilar to 350,000 protein in normal cells, which is missing in AT cell s. Immunoprecipitated protein(s) is capable of phosphorylating I kappa B-alpha in an in vitro kinase assay. However, we did not observe a ph osphatidyl-3 kinase or a DNA-dependent protein kinase function by a AT M immunoprecipitates. These data support a protein kinase activity for ATM and suggest a role in NF-kappa B activation.