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Gene Review

PPP2CA  -  protein phosphatase 2, catalytic subunit,...

Homo sapiens

Synonyms: PP2A-alpha, PP2Ac, PP2CA, PP2Calpha, RP-C, ...
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Disease relevance of PPP2CA


Psychiatry related information on PPP2CA

  • METHODS: This prospective, naturalistic study of the treatment of postnatal depression compared 30 women treated at a specialised psychiatric day hospital with 30 women treated using routine primary care (RPC) [5].
  • RESULTS: Compared with RPC, the PEG significantly reduced the level of depressive symptoms, but had no impact on psychosocial outcome [6].

High impact information on PPP2CA

  • Elevated PP2Ac causes hypophosphorylation of MAPs, a pathological mechanism that is consistent with the OS phenotype [7].
  • By deletion analysis, the binding domains were found to be located within the 50 N-terminal amino acids of PP2Ac, and between amino acid residues 338 and 381 in the C-terminal part of human eRF1 [8].
  • In addition to the 36 kDa catalytic subunit (PP2Ac) and established regulatory subunits of 65 kDa (PR65) and 55 kDa (PR55), purified preparations contained two proteins with apparent Mrs of 54 and 55 kDa [8].
  • Our results imply that differential methylation of PP2Ac occurs at the G0/G1 and G1/S boundaries [9].
  • Monospecific and affinity-purified antibodies against both PP2Ac and PR65 show that these proteins are ubiquitously localized in the cytoplasm and the nucleus in nontransformed fibroblasts [9].

Biological context of PPP2CA

  • We demonstrate here that RP-C is identical to the catalytic subunit of cellular protein phosphatase 2A (PP2Ac) [10].
  • We also show that purified RP-C/PP2Ac preferentially stimulates SV40 DNA replication in extracts from early G1 phase cells [10].
  • Other molecular mechanisms that regulate PP2Ac function include phosphorylation, carboxyl methylation, inhibition by intracellular protein inhibitors (I(1)(PP2A) and I(2)(PP2A)), and stimulation by ceramide [11].
  • Detailed analysis of synchronized cells reveals striking changes in the nuclear to cytoplasmic ratio of PP2Ac-specific immunoreactivity albeit the total amounts of neither PP2Ac nor PR65 in each compartment alters significantly during the cell cycle [9].
  • Finally, we demonstrate that the endogenous VDR, PP1c or PP2Ac, and p70(S6k) are present in a ternary complex in vivo, and the interaction of p70(S6k) with the VDR-PP complex is modulated by the phosphorylation state of the kinase [12].

Anatomical context of PPP2CA

  • Immunostaining of PP2Ac or of PP2Aa + c overexpressing HPAEC indicated actin cytoskeleton rearrangement [13].
  • Transient overexpression of alpha4 in COS-1 cells had no effect on endogenous PP2Ac protein levels but significantly increased PP2Ac carboxymethylation and PP2A activity as compared to controls [1].
  • A trimeric protein phosphatase 2A (PP2A(T55)) composed of the catalytic (PP2Ac), structural (PR65/A), and regulatory (PR55/B) subunits was isolated from rabbit skeletal muscle by thiophosphorylase affinity chromatography, and contained two additional proteins of 54 and 55 kDa, respectively [14].
  • Thus, our findings indicate that Hsp90 functions to balance the phosphorylation state of Akt by modulating the ability of Akt to be dephosphorylated by PP2Ac during C2C12 myoblast differentiation [15].

Associations of PPP2CA with chemical compounds


Other interactions of PPP2CA

  • The mRNA level of PP2A beta was markedly decreased within 5 h after addition of ATRA, but there was only a slight increase in the mRNA level of PP2A alpha [22].
  • The interactions of several candidate proteins, such as tuberous sclerosis complex 2, RhoB, R-Ras, and Nm23H2, with PP2Ac, were confirmed by in vitro binding analyses and/or coimmunoprecipitation experiments [23].
  • When matched for activity toward glycogen phosphorylase, PP2A1 was five- to sevenfold more active than PP2A2 and 35-fold to 70-fold more active than the free catalytic subunit (PP2Ac) toward the three CDK-labeled substrates [24].
  • Whole-cell treatments with okadaic acid or calyculin A diminished SERT/PP2Ac associations [25].
  • Both biochemical fractionation and immunofluorescence analysis of detergent-extracted cells revealed that fractions of PP2Ac, PR65, and B55 were tightly associated with vimentin [26].

Analytical, diagnostic and therapeutic context of PPP2CA


  1. Overexpression of the mTOR alpha4 phosphoprotein activates protein phosphatase 2A and increases Stat1alpha binding to PIAS1. Nien, W.L., Dauphinee, S.M., Moffat, L.D., Too, C.K. Mol. Cell. Endocrinol. (2007) [Pubmed]
  2. Protein phosphatase 2A enhances activation of human immunodeficiency virus type 1 by phorbol myristate acetate. Faulkner, N.E., Lane, B.R., Bock, P.J., Markovitz, D.M. J. Virol. (2003) [Pubmed]
  3. Active-site mutations impairing the catalytic function of the catalytic subunit of human protein phosphatase 2A permit baculovirus-mediated overexpression in insect cells. Myles, T., Schmidt, K., Evans, D.R., Cron, P., Hemmings, B.A. Biochem. J. (2001) [Pubmed]
  4. Ligand modulates VDR-Ser/Thr protein phosphatase interaction and p70S6 kinase phosphorylation in a cell-context-dependent manner. Bettoun, D.J., Lu, J., Khalifa, B., Yee, Y., Chin, W.W., Nagpal, S. J. Steroid Biochem. Mol. Biol. (2004) [Pubmed]
  5. When the cradle falls: the treatment of postnatal depression in a psychiatric day hospital compared with routine primary care. Boath, E., Cox, J., Lewis, M., Jones, P., Pryce, A. Journal of affective disorders. (1999) [Pubmed]
  6. A brief psycho-educational group intervention for postnatal depression. Honey, K.L., Bennett, P., Morgan, M. The British journal of clinical psychology / the British Psychological Society. (2002) [Pubmed]
  7. MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation. Trockenbacher, A., Suckow, V., Foerster, J., Winter, J., Krauss, S., Ropers, H.H., Schneider, R., Schweiger, S. Nat. Genet. (2001) [Pubmed]
  8. The catalytic subunit of protein phosphatase 2A associates with the translation termination factor eRF1. Andjelković, N., Zolnierowicz, S., Van Hoof, C., Goris, J., Hemmings, B.A. EMBO J. (1996) [Pubmed]
  9. Differential methylation and altered conformation of cytoplasmic and nuclear forms of protein phosphatase 2A during cell cycle progression. Turowski, P., Fernandez, A., Favre, B., Lamb, N.J., Hemmings, B.A. J. Cell Biol. (1995) [Pubmed]
  10. Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A. Virshup, D.M., Kauffman, M.G., Kelly, T.J. EMBO J. (1989) [Pubmed]
  11. Type 2A protein phosphatase, the complex regulator of numerous signaling pathways. Zolnierowicz, S. Biochem. Pharmacol. (2000) [Pubmed]
  12. A vitamin D receptor-Ser/Thr phosphatase-p70 S6 kinase complex and modulation of its enzymatic activities by the ligand. Bettoun, D.J., Buck, D.W., Lu, J., Khalifa, B., Chin, W.W., Nagpal, S. J. Biol. Chem. (2002) [Pubmed]
  13. Role of protein phosphatase 2A in the regulation of endothelial cell cytoskeleton structure. Tar, K., Csortos, C., Czikora, I., Olah, G., Ma, S.F., Wadgaonkar, R., Gergely, P., Garcia, J.G., Verin, A.D. J. Cell. Biochem. (2006) [Pubmed]
  14. Interaction of nucleoredoxin with protein phosphatase 2A. Lechward, K., Sugajska, E., de Baere, I., Goris, J., Hemmings, B.A., Zolnierowicz, S. FEBS Lett. (2006) [Pubmed]
  15. Hsp90 functions to balance the phosphorylation state of Akt during C2C12 myoblast differentiation. Yun, B.G., Matts, R.L. Cell. Signal. (2005) [Pubmed]
  16. Different oligomeric forms of protein phosphatase 2A activate and inhibit simian virus 40 DNA replication. Cegielska, A., Shaffer, S., Derua, R., Goris, J., Virshup, D.M. Mol. Cell. Biol. (1994) [Pubmed]
  17. Functional expression of human PP2Ac in yeast permits the identification of novel C-terminal and dominant-negative mutant forms. Evans, D.R., Myles, T., Hofsteenge, J., Hemmings, B.A. J. Biol. Chem. (1999) [Pubmed]
  18. The structural requirements for ceramide activation of serine-threonine protein phosphatases. Chalfant, C.E., Szulc, Z., Roddy, P., Bielawska, A., Hannun, Y.A. J. Lipid Res. (2004) [Pubmed]
  19. Downregulation of neuronal cdk5/p35 in opioid addicts and opiate-treated rats: relation to neurofilament phosphorylation. Ferrer-Alcón, M., La Harpe, R., Guimón, J., García-Sevilla, J.A. Neuropsychopharmacology (2003) [Pubmed]
  20. Regulation by glucose and calcium of the carboxylmethylation of the catalytic subunit of protein phosphatase 2A in insulin-secreting INS-1 cells. Palanivel, R., Veluthakal, R., Kowluru, A. Am. J. Physiol. Endocrinol. Metab. (2004) [Pubmed]
  21. PAK is regulated by PI3K, PIX, CDC42, and PP2Calpha and mediates focal adhesion turnover in the hyperosmotic stress-induced p38 pathway. Chan, P.M., Lim, L., Manser, E. J. Biol. Chem. (2008) [Pubmed]
  22. Down-regulation by retinoic acid of the catalytic subunit of protein phosphatase type 2A during granulocytic differentiation of HL-60 cells. Tawara, I., Nishikawa, M., Morita, K., Kobayashi, K., Toyoda, H., Omay, S.B., Shima, H., Nagao, M., Kuno, T., Tanaka, C. FEBS Lett. (1993) [Pubmed]
  23. Identification of proteins interacting with the catalytic subunit of PP2A by proteomics. Lee, W.J., Kim, D.U., Lee, M.Y., Choi, K.Y. Proteomics (2007) [Pubmed]
  24. Protein phosphatase 2A1 is the major enzyme in vertebrate cell extracts that dephosphorylates several physiological substrates for cyclin-dependent protein kinases. Ferrigno, P., Langan, T.A., Cohen, P. Mol. Biol. Cell (1993) [Pubmed]
  25. Cocaine and antidepressant-sensitive biogenic amine transporters exist in regulated complexes with protein phosphatase 2A. Bauman, A.L., Apparsundaram, S., Ramamoorthy, S., Wadzinski, B.E., Vaughan, R.A., Blakely, R.D. J. Neurosci. (2000) [Pubmed]
  26. Vimentin dephosphorylation by protein phosphatase 2A is modulated by the targeting subunit B55. Turowski, P., Myles, T., Hemmings, B.A., Fernandez, A., Lamb, N.J. Mol. Biol. Cell (1999) [Pubmed]
  27. Differential inhibition and posttranslational modification of protein phosphatase 1 and 2A in MCF7 cells treated with calyculin-A, okadaic acid, and tautomycin. Favre, B., Turowski, P., Hemmings, B.A. J. Biol. Chem. (1997) [Pubmed]
  28. Bestrophin interacts physically and functionally with protein phosphatase 2A. Marmorstein, L.Y., McLaughlin, P.J., Stanton, J.B., Yan, L., Crabb, J.W., Marmorstein, A.D. J. Biol. Chem. (2002) [Pubmed]
  29. Controlled evaluation of rural regional perinatal care: developmental and neurologic outcomes at 1 year. Siegel, E., Gillings, D., Campbell, S., Guild, P. Pediatrics (1986) [Pubmed]
  30. When the cradle falls II: The cost-effectiveness of treating postnatal depression in a psychiatric day hospital compared with routine primary care. Boath, E., Major, K., Cox, J. Journal of affective disorders. (2003) [Pubmed]
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