protein phosphatase 2


Summary: A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.

Top Publications

  1. Wadzinski B, Wheat W, Jaspers S, Peruski L, Lickteig R, Johnson G, et al. Nuclear protein phosphatase 2A dephosphorylates protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation. Mol Cell Biol. 1993;13:2822-34 pubmed
    ..Nuclear PP2A appears to be the primary phosphatase that dephosphorylates PKA-phosphorylated CREB. ..
  2. Sontag E, Nunbhakdi Craig V, Lee G, Bloom G, Mumby M. Regulation of the phosphorylation state and microtubule-binding activity of Tau by protein phosphatase 2A. Neuron. 1996;17:1201-7 pubmed
    ..Taken together, these results support the hypothesis that PP2A controls the phosphorylation state of tau in vivo. ..
  3. Ramírez Valadez K, Vázquez Victorio G, Macias Silva M, Gonzalez Espinosa C. Fyn kinase mediates cortical actin ring depolymerization required for mast cell migration in response to TGF-? in mice. Eur J Immunol. 2017;47:1305-1316 pubmed publisher
    ..Our results show that Fyn kinase is an important positive effector of TGF-?-induced chemotaxis through the control of PP2A activity and this is relevant to pathological processes that are related to TGF-?-dependent mast cell migration. ..
  4. Abraham D, Podar K, Pacher M, Kubicek M, Welzel N, Hemmings B, et al. Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation. J Biol Chem. 2000;275:22300-4 pubmed
    ..The PP2A core heterodimer forms complexes with Raf-1 in vivo and in vitro. These data identify PP2A as a positive regulator of Raf-1 activation and are the first indication that PP2A may support the activation of an associated kinase. ..
  5. Bollen M. Cell cycle: It takes three to find the exit. Nature. 2015;517:29-30 pubmed publisher
  6. Wang J, Pei L, Jin Z, Zhang K, Zhang J. Overexpression of the protein phosphatase 2A regulatory subunit a gene ZmPP2AA1 improves low phosphate tolerance by remodeling the root system architecture of maize. PLoS ONE. 2017;12:e0176538 pubmed publisher
    ..These data reveal the biological function of ZmPP2AA1, provide insights into a linkage between auxin and low Pi responses, and drive new strategies for the efficient utilization of Pi by maize...
  7. Hein J, Hertz E, Garvanska D, Kruse T, Nilsson J. Distinct kinetics of serine and threonine dephosphorylation are essential for mitosis. Nat Cell Biol. 2017;19:1433-1440 pubmed publisher
    ..Altogether, the findings of our work reveal that the inherent residue preference of a protein phosphatase can provide temporal regulation in biological processes. ..
  8. Awad A, Venkataramanan S, Nag A, Galivanche A, Bradley M, Neves L, et al. Chromatin-remodeling SWI/SNF complex regulates coenzyme Q6 synthesis and a metabolic shift to respiration in yeast. J Biol Chem. 2017;292:14851-14866 pubmed publisher
  9. Wright K, Du H, Massiah M. Structural and functional observations of the P151L MID1 mutation reveal alpha4 plays a significant role in X-linked Opitz Syndrome. FEBS J. 2017;284:2183-2193 pubmed publisher

More Information


  1. Pradhan S, Vijayan K. Lipid rafts contribute to agonist-induced serine/threonine phosphatase activation and platelet aggregation. J Thromb Haemost. 2013;11:1612-5 pubmed publisher
  2. Guo S, Chen C, Ji F, Mao L, Xie Y. PP2A catalytic subunit silence by microRNA-429 activates AMPK and protects osteoblastic cells from dexamethasone. Biochem Biophys Res Commun. 2017;487:660-665 pubmed publisher
    ..Such effect by miR-429 was again abolished with AMPK?1 silence or mutation. Together, we propose that PP2A-c silence by miR-429 activates AMPK and protects osteoblastic cells from Dex. ..
  3. Andjelkovic M, Jakubowicz T, Cron P, Ming X, Han J, Hemmings B. Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors. Proc Natl Acad Sci U S A. 1996;93:5699-704 pubmed
    ..Taken together the results suggest that RAC-PK is a component of a signaling pathway regulated by phosphatidylinositol (PI) 3-kinase, whose action is required for RAC-PK activation by phosphorylation. ..
  4. Watanabe D, Takagi H. Pleiotropic functions of the yeast Greatwall-family protein kinase Rim15p: a novel target for the control of alcoholic fermentation. Biosci Biotechnol Biochem. 2017;81:1061-1068 pubmed publisher
    ..Our finding of an in vivo metabolic regulatory mechanism is expected to provide a major breakthrough in yeast breeding technologies for fermentation applications. ..
  5. Kliewer A, Reinscheid R, Schulz S. Emerging Paradigms of G Protein-Coupled Receptor Dephosphorylation. Trends Pharmacol Sci. 2017;38:621-636 pubmed publisher
    ..These findings reveal unappreciated cellular sites and regulatory functions of receptor dephosphorylation and call for revised models of the GPCR activation/deactivation cycle. ..
  6. Santarlasci V, Mazzoni A, Capone M, Rossi M, Maggi L, Montaini G, et al. Musculin inhibits human T-helper 17 cell response to interleukin 2 by controlling STAT5B activity. Eur J Immunol. 2017;47:1427-1442 pubmed publisher
    ..Thus, our findings identify an additional mechanism responsible for the limited expansion of human Th17 cells, and could provide a further explanation for the rarity of these cells in inflamed tissues. ..
  7. Lee S, Rodriguez Bravo V, Kim H, Datta S, Foley E. The PP2AB56 phosphatase promotes the association of Cdc20 with APC/C in mitosis. J Cell Sci. 2017;130:1760-1771 pubmed publisher
    ..A mitotic phosphorylation site on Cdc20, known to be a substrate of PP2AB56, modulates APC/CCdc20 assembly. These results elucidate the contributions of PP2AB56 towards completion of mitosis. ..
  8. Kumazoe M, Yamashita M, Nakamura Y, Takamatsu K, Bae J, Yamashita S, et al. Green Tea Polyphenol EGCG Upregulates Tollip Expression by Suppressing Elf-1 Expression. J Immunol. 2017;199:3261-3269 pubmed publisher
    ..These data support EGCG and a cGMP inducer as potential candidate suppressors of TLR4 signaling. ..
  9. Bott A, Erdem N, Lerrer S, Hotz Wagenblatt A, Breunig C, Abnaof K, et al. miRNA-1246 induces pro-inflammatory responses in mesenchymal stem/stromal cells by regulating PKA and PP2A. Oncotarget. 2017;8:43897-43914 pubmed publisher
    ..Our data shows that miR-1246 acts as both key-enhancer of pro-inflammatory responses in MSCs and putative oncomiR in breast cancer, suggesting its influence on cancer-related inflammation and breast cancer progression. ..
  10. Pengo N, Agrotis A, Prak K, Jones J, Ketteler R. A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B. Nat Commun. 2017;8:294 pubmed publisher
    ..Here the authors show that ULK1-mediated phosphorylation and PP2A-mediated dephosphorylation of ATG4 regulates its cellular activity to control LC3 processing. ..
  11. Stutz A, Kolbe C, Stahl R, Horvath G, Franklin B, van Ray O, et al. NLRP3 inflammasome assembly is regulated by phosphorylation of the pyrin domain. J Exp Med. 2017;214:1725-1736 pubmed publisher
    ..These results propose that the balance between kinases and phosphatases acting on the NLRP3 PYD is critical for NLRP3 activation. ..
  12. Garcia M, Grasso D, López Millán M, Hamidi T, Loncle C, Tomasini R, et al. IER3 supports KRASG12D-dependent pancreatic cancer development by sustaining ERK1/2 phosphorylation. J Clin Invest. 2014;124:4709-22 pubmed publisher
    ..Together, our data indicate that IER3 supports KRASG12D-associated oncogenesis in the pancreas by sustaining ERK1/2 phosphorylation via phosphatase PP2A inhibition. ..
  13. Sangodkar J, Perl A, Tohme R, Kiselar J, Kastrinsky D, Zaware N, et al. Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth. J Clin Invest. 2017;127:2081-2090 pubmed publisher
    ..Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins. ..
  14. Anglesio M, Papadopoulos N, Ayhan A, Nazeran T, Noe M, Horlings H, et al. Cancer-Associated Mutations in Endometriosis without Cancer. N Engl J Med. 2017;376:1835-1848 pubmed publisher
    ..Ten of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions. ..
  15. Chen P, Chu P, Tung S, Liu C, Tsai Y, Lin Y, et al. Overexpression of phosphoprotein phosphatase 2A predicts worse prognosis in patients with breast cancer: a 15-year follow-up. Hum Pathol. 2017;66:93-100 pubmed publisher
    ..012). Our data revealed that high p-PP2A expression is positively associated with HER2, Ki-67, and p-AKT expression. High p-PP2A expression correlates with poor clinical outcomes in breast cancer, especially in patients with TNBC. ..
  16. . Large-scale discovery of novel genetic causes of developmental disorders. Nature. 2015;519:223-8 pubmed publisher
    ..Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders. ..
  17. Wang J, Okkeri J, Pavic K, Wang Z, Kauko O, Halonen T, et al. Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56. EMBO Rep. 2017;18:437-450 pubmed publisher
    ..These results provide the first structure-function analysis of the interaction of CIP2A with PP2A/B56 and have direct implications for its targeting in cancer therapy. ..
  18. Nicholson L. Mechanism of midline defect-causing mutation P151L in MID1 revealed. FEBS J. 2017;284:2167-2169 pubmed publisher
    ..Wright et al. show that this mutation retains B-box1 domain structure and E3 ligase activity (star) but blocks interaction with ?4, indicating disruption of the MID1-?4-PP2Ac complex. ..
  19. Hong J, Chu M, Qian L, Wang J, Guo Y, Xu D. Fibrillar Type I Collagen Enhances the Differentiation and Proliferation of Myofibroblasts by Lowering ?2?1 Integrin Expression in Cardiac Fibrosis. Biomed Res Int. 2017;2017:1790808 pubmed publisher
  20. Kim M, Choe M, Yoon Y, Ahn J, Yoo M, Jung K, et al. Antihelminthic drug niclosamide inhibits CIP2A and reactivates tumor suppressor protein phosphatase 2A in non-small cell lung cancer cells. Biochem Pharmacol. 2017;144:78-89 pubmed publisher
    ..This provided strong evidence for the potential use of niclosamide asa PP2A-activating drug in the clinical treatment of NSCLC. ..
  21. Shi Q, Xiong B, Zhong J, Wang H, Ma D, Miao C. MFHAS1 suppresses TLR4 signaling pathway via induction of PP2A C subunit cytoplasm translocation and inhibition of c-Jun dephosphorylation at Thr239. Mol Immunol. 2017;88:79-88 pubmed publisher
  22. Cohen P, Alemany S, Hemmings B, Resink T, Stralfors P, Tung H. Protein phosphatase-1 and protein phosphatase-2A from rabbit skeletal muscle. Methods Enzymol. 1988;159:390-408 pubmed
  23. Khew Goodall Y, Hemmings B. Tissue-specific expression of mRNAs encoding alpha- and beta-catalytic subunits of protein phosphatase 2A. FEBS Lett. 1988;238:265-8 pubmed
    ..In addition to the 2 kb mRNA generally expressed, rat tissues also express a 2.8 kb mRNA related to 2A alpha and a 1.3 kb mRNA related to 2A beta. ..
  24. Varadkar P, Abbasi F, Takeda K, Dyson J, McCright B. PP2A-B56? is required for an efficient spindle assembly checkpoint. Cell Cycle. 2017;16:1210-1219 pubmed publisher
    ..We also provide data that show the intracellular locations of the B56 subunits varies between family members, which is consistent with the hypothesis that they are not completely functionally redundant. ..
  25. Wu H, Lay I, Shibu M, Ho T, Cheng S, Lin C, et al. Zanthoxylum avicennae extract enhances GSK-3? to attenuate ?-catenin via phosphatase 2A to block metastatic effects of HA22T cells and hepatocellular carcinoma xenografted nude mice. Environ Toxicol. 2017;32:2133-2143 pubmed publisher
    ..In conclusion, both in vitro and in vivo models clearly demonstrated that YBBE inhibits ?-catenin involved metastatic signaling in highly metastatic HA22T cells through PP2A activation. ..
  26. Hemmings H, Nairn A, Elliott J, Greengard P. Synthetic peptide analogs of DARPP-32 (Mr 32,000 dopamine- and cAMP-regulated phosphoprotein), an inhibitor of protein phosphatase-1. Phosphorylation, dephosphorylation, and inhibitory activity. J Biol Chem. 1990;265:20369-76 pubmed
    ..These findings support the hypothesis that a 30-amino acid domain in the NH2-terminal region of phospho-DARPP-32 is sufficient for the inhibition of protein phosphatase-1. ..
  27. Zheng M, Zou C, Li M, Huang G, Gao Y, Liu H. Folic Acid Reduces Tau Phosphorylation by Regulating PP2A Methylation in Streptozotocin-Induced Diabetic Mice. Int J Mol Sci. 2017;18: pubmed publisher
    ..These results support that folic acid can serve as a multitarget neuronal therapeutic agent for treating diabetes-associated cognitive dysfunction. ..
  28. Tobisawa T, Yano T, Tanno M, Miki T, Kuno A, Kimura Y, et al. Insufficient activation of Akt upon reperfusion because of its novel modification by reduced PP2A-B55α contributes to enlargement of infarct size by chronic kidney disease. Basic Res Cardiol. 2017;112:31 pubmed publisher
  29. Shizu R, Osabe M, Perera L, Moore R, Sueyoshi T, Negishi M. Phosphorylated Nuclear Receptor CAR Forms a Homodimer To Repress Its Constitutive Activity for Ligand Activation. Mol Cell Biol. 2017;37: pubmed publisher
    ..Thus, the homodimer-monomer conversion is the underlying molecular mechanism that regulates CAR activation, by placing phosphorylated threonine 38 as the common target for both direct and indirect activation of CAR. ..
  30. Armstrong M, Sestak S, Ali A, Sagini H, Brown M, Baty K, et al. Bypass of Activation Loop Phosphorylation by Aspartate 836 in Activation of the Endoribonuclease Activity of Ire1. Mol Cell Biol. 2017;37: pubmed publisher
    ..By itself, the D836A mutation does not confer a phenotype. These data argue that D836 can partially substitute for activation loop phosphorylation in activation of the endoribonuclease domain of Ire1. ..
  31. Velmurugan B, Lee C, Chiang S, Hua C, Chen M, Lin S, et al. PP2A deactivation is a common event in oral cancer and reactivation by FTY720 shows promising therapeutic potential. J Cell Physiol. 2018;233:1300-1311 pubmed publisher
    ..All our results suggest that PP2A is frequently deactivated in oral cancer and determines poor outcome, restoring its expression by FTY720 can be an alternative therapeutic approach in OSCC. ..
  32. Mahmoud S, Planes M, Cabedo M, Trujillo C, Rienzo A, Caballero Molada M, et al. TOR complex 1 regulates the yeast plasma membrane proton pump and pH and potassium homeostasis. FEBS Lett. 2017;591:1993-2002 pubmed publisher
    ..Tco89 does not affect Pma1 activity but activates K+ transport. ..
  33. Lin L, Lo L, Lyu Q, Lai K. Determination of dendritic spine morphology by the striatin scaffold protein STRN4 through interaction with the phosphatase PP2A. J Biol Chem. 2017;292:9451-9464 pubmed publisher
    ..Our findings have therefore unraveled the local expression of STRN4 as a novel mechanism for the control of dendritic spine morphology. ..
  34. Ferrari E, Bruhn C, Peretti M, Cassani C, Carotenuto W, Elgendy M, et al. PP2A Controls Genome Integrity by Integrating Nutrient-Sensing and Metabolic Pathways with the DNA Damage Response. Mol Cell. 2017;67:266-281.e4 pubmed publisher
    ..Our observations imply that metabolic changes affect genome integrity and may help with exploiting therapeutic options and repositioning known drugs. ..
  35. Gutierrez A, Pan L, Groen R, Baleydier F, Kentsis A, Marineau J, et al. Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia. J Clin Invest. 2014;124:644-55 pubmed publisher
    ..Furthermore, these data suggest that pharmacologic PP2A activation in T-ALL and other cancers driven by hyperphosphorylated PP2A substrates has therapeutic potential. ..
  36. Yeh P, Chang C. A novel function of twins, B subunit of protein phosphatase 2A, in regulating actin polymerization. PLoS ONE. 2017;12:e0186037 pubmed publisher
    ..This work opens a new avenue for exploring the biological functions of a PP2A regulator, twins, in cytoskeleton regulation...
  37. Henriksson E, Säll J, Gormand A, Wasserstrom S, Morrice N, Fritzen A, et al. SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes. J Cell Sci. 2015;128:472-86 pubmed
    ..Downstream, SIK2 increases GLUT4 levels and glucose uptake in adipocytes. ..
  38. Parang B, Kaz A, Barrett C, Short S, Ning W, Keating C, et al. BVES regulates c-Myc stability via PP2A and suppresses colitis-induced tumourigenesis. Gut. 2017;66:852-862 pubmed publisher
    ..Loss of BVES promotes inflammatory tumourigenesis through dysregulation of Wnt signalling and the oncogene c-Myc. BVES promoter methylation status may serve as a CAC biomarker. ..