The catalytic subunit of protein phosphatase 2A (PP2A) is inactivated by in vitro phosphorylation of Tyr-307 by receptor and nonreceptor protein tyrosine kinases. The catalytic subunit of PP2A is phosphorylated by tyrosine-specific protein kinases and associates with a variety of regulatory subunits. Phosphorylation is enhanced in the presence of the phosphatase inhibitor okadaic acid, consistent with an autodephosphorylation reaction. Phosphorylation is catalyzed by p60v-src, p56lck, epidermal growth factor receptors, and insulin receptors. Transient deactivation of PP2A might enhance transmission of cellular signals through kinase cascades within cells. In eukaryotes, the phosphorylation and dephosphorylation of proteins on serine and threonine residues is an essential means of regulating a broad range of cellular functions, including cell division, homeostasis and apoptosis. A group of proteins that are intimately involved in this process are the protein phosphatases.
Background References
1. Lei X et al. PP2A and tumor radiotherapy. Hereditas. 2020 Aug
2. Ronk H et al. Targeting PP2A for cancer therapeutic modulation. Cancer Biol Med. 2022 Nov
Sequence Similarity
Belongs to the PPP phosphatase family. PP-1 subfamily.
Post-translational Modification
Reversibly methyl esterified on Leu-309 by leucine carboxyl methyltransferase 1 (LCMT1) and protein phosphatase methylesterase 1 (PPME1). Carboxyl methylation influences the affinity of the catalytic subunit for the different regulatory subunits, thereby modulating the PP2A holoenzyme's substrate specificity, enzyme activity and cellular localization.; Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation.; May be monoubiquitinated by NOSIP.
Subcellular Location
Cytoplasm, Nucleus, Chromosome, centromere, cytoskeleton, spindle pole.
Western blot analysis of PP2A alpha + beta on different lysates with Mouse anti-PP2A alpha + beta antibody (M1603-4) at 1/2,000 dilution.
Lane 1: A431 cell lysate (10 µg/Lane) Lane 2: 293T cell lysate (10 µg/Lane) Lane 3: NIH/3T3 cell lysate (10 µg/Lane) Lane 4: F9 cell lysate (10 µg/Lane) Lane 5: PC-12 cell lysate (10 µg/Lane) Lane 6: Mouse brain tissue lysate (20 µg/Lane) Lane 7: Rat brain tissue lysate (20 µg/Lane)
Predicted band size: 36 kDa Observed band size: 36 kDa
Exposure time: 2 seconds; ECL: K1801;
4-20% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (M1603-4) at 1/2,000 dilution was used in 5% NFDM/TBST at 4℃ overnight. Goat Anti-Mouse IgG - HRP Secondary Antibody (HA1006) at 1/50,000 dilution was used for 1 hour at room temperature.
ICC staining PP2A(alpha+beta) (green) in Hela cells. The nuclear counter stain is DAPI (blue). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS.
ICC staining PP2A(alpha+beta) (green) in MCF-7 cells. The nuclear counter stain is DAPI (blue). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS.
ICC staining PP2A(alpha+beta) (green) in SHG-44 cells. The nuclear counter stain is DAPI (blue). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS.
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