Key Specifications Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|B, H, M, Po, R, Rb, Xn||IHC, IP, WB||M||Ascites||Monoclonal Antibody|
|Description||Anti-PP2A Antibody, B subunit, clone 2G9|
|Presentation||0.1M Tris-glycine, pH 7.4, 0.15M NaCl, 0.05% sodium azide and glycerol to 30%|
|Application||Detect PP2A using this Anti-PP2A Antibody, B subunit, clone 2G9 validated for use in IH, IP & WB.|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||2 years at -20°C|
|Material Size||200 µL|
|Anti-PP2A, B subunit, clone 2G9 (mouse ascites) - 2326374||2326374|
|Anti-PP2A, B subunit, clone 2G9 (mouse ascites) - DAM1437260||DAM1437260|
|Anti-PP2A, B subunit, clone 2G9 - 20265||20265|
|Anti-PP2A, B subunit, clone 2G9 - DAM1810801||DAM1810801|
|Anti-PP2A, B subunit, clone 2G9 - JBC1940047||JBC1940047|
|Anti-PP2A, B subunit, clone 2G9 -2539262||2539262|
|Anti-PP2A, B subunit, clone 2G9 -2628322||2628322|
|Anti-PP2A, B subunit, clone 2G9 -2648599||2648599|
|Reference overview||Application||Pub Med ID|
|Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers. |
Williams, BC; Filter, JJ; Blake-Hodek, KA; Wadzinski, BE; Fuda, NJ; Shalloway, D; Goldberg, ML
eLife 3 e01695 2014
During M phase, Endosulfine (Endos) family proteins are phosphorylated by Greatwall kinase (Gwl), and the resultant pEndos inhibits the phosphatase PP2A-B55, which would otherwise prematurely reverse many CDK-driven phosphorylations. We show here that PP2A-B55 is the enzyme responsible for dephosphorylating pEndos during M phase exit. The kinetic parameters for PP2A-B55's action on pEndos are orders of magnitude lower than those for CDK-phosphorylated substrates, suggesting a simple model for PP2A-B55 regulation that we call inhibition by unfair competition. As the name suggests, during M phase PP2A-B55's attention is diverted to pEndos, which binds much more avidly and is dephosphorylated more slowly than other substrates. When Gwl is inactivated during the M phase-to-interphase transition, the dynamic balance changes: pEndos dephosphorylated by PP2A-B55 cannot be replaced, so the phosphatase can refocus its attention on CDK-phosphorylated substrates. This mechanism explains simultaneously how PP2A-B55 and Gwl together regulate pEndos, and how pEndos controls PP2A-B55. DOI: http://dx.doi.org/10.7554/eLife.01695.001.
|Altered protein phosphatase 2A methylation and Tau phosphorylation in the young and aged brain of methylenetetrahydrofolate reductase (MTHFR) deficient mice. |
Sontag, JM; Wasek, B; Taleski, G; Smith, J; Arning, E; Sontag, E; Bottiglieri, T
Frontiers in aging neuroscience 6 214 2014
Common functional polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in folate and homocysteine metabolism, influence risk for a variety of complex disorders, including developmental, vascular, and neurological diseases. MTHFR deficiency is associated with elevation of homocysteine levels and alterations in the methylation cycle. Here, using young and aged Mthfr knockout mouse models, we show that mild MTHFR deficiency can lead to brain-region specific impairment of the methylation of Ser/Thr protein phosphatase 2A (PP2A). Relative to wild-type controls, decreased expression levels of PP2A and leucine carboxyl methyltransferase (LCMT1) were primarily observed in the hippocampus and cerebellum, and to a lesser extent in the cortex of young null Mthfr (-/-) and aged heterozygous Mthfr (+/-) mice. A marked down regulation of LCMT1 correlated with the loss of PP2A/Bα holoenzymes. Dietary folate deficiency significantly decreased LCMT1, methylated PP2A and PP2A/Bα levels in all brain regions examined from aged Mthfr (+/+) mice, and further exacerbated the regional effects of MTHFR deficiency in aged Mthfr (+/-) mice. In turn, the down regulation of PP2A/Bα was associated with enhanced phosphorylation of Tau, a neuropathological hallmark of Alzheimer's disease (AD). Our findings identify hypomethylation of PP2A enzymes, which are major CNS phosphatases, as a novel mechanism by which MTHFR deficiency and Mthfr gene-diet interactions could lead to disruption of neuronal homeostasis, and increase the risk for a variety of neuropsychiatric disorders, including age-related diseases like sporadic AD.
|Protein phosphatase 2A regulates estrogen receptor alpha (ER) expression through modulation of ER mRNA stability. |
Keen, JC; Zhou, Q; Park, BH; Pettit, C; Mack, KM; Blair, B; Brenner, K; Davidson, NE
The Journal of biological chemistry 280 29519-24 2005
Protein phosphatase 2A (PP2A) is a ubiquitously expressed member of the serine-threonine phosphatase family that is involved in regulation of many cellular processes including transcription, translation, cellular metabolism, and apoptosis. Because of a correlation between PP2A and estrogen receptor alpha (ER) expression in several human breast cancer cell lines, the effect of PP2A on regulation of ER expression in the human breast cancer cell line MCF-7 was studied. Inhibition of PP2A using the pharmacologic inhibitor okadaic acid at 250 nm for 16 h resulted in a 60% reduction in PP2A activity in MCF-7 cells concurrent with a 75% reduction in ER mRNA and protein expression. Similar results were obtained with a small interfering RNA probe that specifically inhibited PP2A expression. ER promoter studies showed that regulation of ER through the PP2A pathway did not occur through transcriptional activation. Rather, PP2A mediated ER expression through modulation of ER mRNA stability through degradation of ER mRNA, reversible with concomitant treatment with the proteasomal inhibitor MG 132. These data suggest a novel pathway controlling ER expression resulting from the activation of PP2A, potentially providing a novel therapeutic target.
|Altering the holoenzyme composition and substrate specificity of protein phosphatase 2A |
Fellner, T., et al
Methods Enzymol, 366:187-203 (2003) 2003
|Bestrophin interacts physically and functionally with protein phosphatase 2A |
Marmorstein, L. Y., et al
J Biol Chem, 277:30591-7 (2002) 2002
|Protein phosphatase 2A subunit assembly: the catalytic subunit carboxy terminus is important for binding cellular B subunit but not polyomavirus middle tumor antigen. |
Ogris, E, et al.
Oncogene, 15: 911-7 (1997) 1997
The carboxy terminus of protein phosphatase 2A (PP2A) catalytic subunit is highly conserved. Seven out of the last nine residues, including two potential in vivo phosphorylation sites, threonine 304 and tyrosine 307, are completely invariant in all known PP2As. Mutational analysis of the carboxy terminus in vivo was facilitated by efficient immunoprecipitation of trimeric PP2A holoenzyme via an epitope-tagged catalytic subunit. The results indicate that the catalytic subunit carboxy terminus is important for complex formation with the PP2A 55 kDa regulatory B subunit, but not with polyomavirus oncogene, middle tumor antigen (MT), a viral B-type regulatory subunit. Replacing catalytic subunit threonine 304 or tyrosine 307 with a negatively charged amino acid abolished binding of the B subunit to the dimeric enzyme core and altered substrate specificity. Certain other amino acid substitutions of different size and/or charge also abolished or greatly reduced B subunit binding. Substitution of alanine at position 304 or phenylalanine at position 307 did not dramatically reduce B subunit binding or phosphatase activity in vitro, yet the latter substitutions are not found in naturally occurring PP2As. Thus, the wild-type residues are important for a yet unknown function in vivo. Additionally, deleting the carboxy terminal nine amino acids inhibited binding of the B subunit to the dimeric enzyme core, indicating a requirement for one or more of these amino acids for complex formation. MT interaction with the dimeric PP2A enzyme core was not inhibited by any of these mutations. Finally, unlike B subunit, MT does not activate the phosphatase activity of the PP2A heterodimer towards cdc2-phosphorylated histone H1.