PP2A A SubunitSource: Recombinant HumanPurity: > 90% by SDS-PAGE, apparent Mr ~ 65-kDaSupplied: 1 μg in 50 μl of 50 mM Tis-HCl pH 7.0 buffer containing 0.1 mM phenylmethanesulfonyl fluoride, 14 mM β-mercaptoethanol, 1 mM EDTA and 50% glycerol. Maintain in aliquots at -70°C. Avoid repeated thawing.Synonyms: Regulatory 65 kDa A Subunit of Protein Phosphatase 2A; PR65Background: The A PR65 subunit of PP2A serves as a scaffolding molecule to coordinate the assembly of the catalytic (PP2AC) and variable B subunits. This generates functionally diverse heterotrimers of the phosphatase. The A subunit contains 15 tandemly-repeated HEAT sequences which may participate in its function as a scaffolding molecule. The A subunit also serves to regulate the substrate selectivity of PP2AC and allosterically modulates its polycation response. Association of recombinant A subunit with PP2AC is relatively tight (apparent KD ~ 85 pM) and leads to marked suppression of phosphatase activity with several phosphoproteins substrates. By contrast, suppression of PP2A activity is markedly less with several less-structured or smaller substrates such as phosphopeptides. The affinity of the A subunit for PP2AC is diminished by almost 100-fold following introduction of a glutamate at position 416. This indicates that the basic motif in this region of the protein may be important for its interaction with PP2AC. Some evidence indicates a role for the A subunit in disease. For example, at least four low frequency mutations in genes encoding the A subunit with altered affinity for PP2AC have been identified in several different human cancers. Additionally, overexpression of the A subunit in rat embryo fibroblasts leads to multinucleated cells.References: Eur J Biochem 267: 5209  Eur J Biochem 248: 200