Phospho-ATM (Ser1981) Monoclonal Antibody (10H11.E12), eBioscience™, Invitrogen™

Description

• The phosphatidylinositol kinase (PIK) family members fall into two distinct subgroups
• The first subgroup contains proteins such as the PI 3- and PI 4-kinases and the second group comprises the PIK-related kinases
• The PIK-related kinases include Atm, DNA-PKCS and FRAP
• These proteins have in common a region of homology at their carboxy-termini that is not present in the PI 3- and PI 4-kinases
• The Atm gene is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) that is characterized by cerebellar degeneration (ataxia) and the appearance of dilated blood vessels (telangiec-tases) in the conjunctivae of the eyes
• AT cells are hypersensitive to ionizing radiation, impaired in mediating the inhibition of DNA synthesis and display delays in p53 induction
• Ataxia-telangiectasia Mutated (ATM) is a protein that belongs to the PI3/PI4 kinase family
• Ataxia-telangiectasia is a rare autosomal recessive disorder characterized by progressive neurologic degeneration, immunologic deficiency, and an increased risk of lymphoid cancer
• The ATM gene codes for a protein belonging to the phosphoinositide 3-kinase (PI3K) superfamily
• ATM phosphorylates proteins instead of lipid and has many downstream targets that act as cell-cycle regulators including: P53, Mdm2, BRCA1, and SMC1
• The ATM protein is responsible for repairing double-stranded DNA breaks that occur because of ionizing radiation and other mutagens
• The ATM’s C-terminal region has extensive homology to the catalytic domains of phosphatidylinositol 3-kinases (PI3 kinases)
• Studies have shown that ATM becomes autophosphorylated and upregulated by exposure to ionizing radiation
• AT cells are hypersensitive to ionizing radiation, impaired in mediating the inhibition of DNA synthesis and display delays in p53 induction
• Further, DNA damage caused by ionizing irradiation activates ATM-kinase, leading to a cascade of kinase reactions that regulate cell cycle, apoptosis, and DNA damage repair
• Studies have linked ATM to apoptosis along with Nbs1 and Chk2 in the E2F1 pathway.