Ataxia-telangiectasia (A-T) is a recessive childhood disease caused by mutations in the ATM (AT-mutated) gene. Symptoms include neurological abnormalities that cause unsteady posture, dilated blood vessels, infertility, radiation sensitivity, immune deficiencies and lymphoid malignancies. It appears that the diverse defects seen in ATM null mammals are manifestations of disparate signal transduction defects. The ATM protein is related to a family of proteins through a c-terminal phoshatidylinositol 3-kinase (PI3-kinase) domain. ATM also shares sequence homology with portions of the yeast RAD3 gene. The main role of ATM appears to be induction of a DNA-damage control pathway in response to genotoxic insults, such as ionizing radiation or anti-tumor medications and the programmed DNA breaks of meiosis.
Ataxia telangiectasia mutated kinase (ATM) and ataxia telangiectasia and Rad3-related kinase (ATR) are related kinases that regulate cell cycle checkpoints and DNA repair. ATM activates p53, increasing the p21Cip1 levels, thus blocking activation of cdk2. That results in Rb hypophosphorylation and blockage of the G1/S transition. Separately, ATM also phosphorylates and activates Chk1, which phosphorylates cdc25C, preventing it from phosphorylating the inhibitory phosphotyrosine residue on cdc2/cdk1, thus preventiing the G2/M transition.
The identified substrates for ATM are p53, p95/NBS1, MDM2, Chk2, BRCA1, CtIP, 4E-BP1 and Chk1. The essential requirement for the substrates of ATM/ATR is S*/T*Q. Hydrophobic amino acids at positions -3 and -1, and negatively charged amino acids at position +1 are positive determinants for substrate recognition by these kinases. Positively charged residues surrounding the S/TQ are negative determinants for substrate phosphorylation. The complex phenotype of AT cells suggests that it must have other cellular substrates as well.
Applications
Suitable for use in Western Blot and Immunoprecipitation (reported). Other applications not tested.
Recommended Dilution
Western Blot: 1:500 detects ATM in a nuclear extract from Raji cells. Raji nuclear extract was resolved by electrophoresis, transferred to nitrocellulose and probed with anti-ATM. Proteins were visualized using a goat antimouse secondary antibody conjugated to HRP and a chemiluminescence detection system.
Optimal dilutions to be determined by the researcher.
Storage and Stability
May be stored at 4°C for short-term only. For long-term storage and to avoid repeated freezing and thawing, add sterile glycerol (40-50%), aliquot and store at -20°C or colder. Aliquots are stable for at least 12 months at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
Immunogen
Full-length human ATM.
Form
Supplied as a liquid, 0.05% sodium azide.
Specificity
Recognizes human ATM, Mr 350kD.
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