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.
In order to better understand the kinase and identify substrates for ATM and the related kinase ATR, we have antibodies that recognize phosphorylated serine or threonine in S*/T*Q motifs.
As shown by ELISA, Phospho-(Ser/Thr) ATM/ATR Substrate Antibody is specific for phosphorylated ATM/ATR substrates.
Applications:Suitable for use in Western Blot.
Other applications not tested.
Recommended Dilution:Western Blot: 1:500-1:1,000Optimal dilutions to be determined by the researcher.
Storage and Stability:May be stored at 4°C for short-term only.
Aliquot to avoid repeated freezing and thawing.
Store at -20°C.
Aliquots are stable for at least 12 months.
For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
仕様
Size:50ug
Host:rabbit
Source Antibody:human
Grade:Affinity Purified
Purity:Purified by immunoaffinity chromatography.
Form:Supplied as a liquid in PBS (without Mg2+ and Ca2+), pH 7.4, 150mM sodium chloride, 0.02% sodium azide, 50% glycerol.
Specificity:Recognizes human ATM. Species Cross-Reactivity: mouse.
Isotype:IgG
Calc Applications Abbrev:E WB
Calc Crossreactivity:Hu Mo
Immunogen:Synthetic non-phosphopeptide corresponding to human ATM around the phosphorylation site of serine 1981 (E-G-SP-Q-S).