Gene Symbol: PPM1A
Description: protein phosphatase, Mg2+/Mn2+ dependent 1A
Alias: PP2C-ALPHA, PP2CA, PP2Calpha, protein phosphatase 1A, protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform
Species: human
Products:     PPM1A

Top Publications

  1. Takekawa M, Maeda T, Saito H. Protein phosphatase 2Calpha inhibits the human stress-responsive p38 and JNK MAPK pathways. EMBO J. 1998;17:4744-52 pubmed
    ..In this screen, the human protein phosphatase type 2Calpha (PP2Calpha) was found to negatively regulate the HOG1 pathway in yeast...
  2. Lifschitz Mercer B, Sheinin Y, Ben Meir D, Bramante Schreiber L, Leider Trejo L, Karby S, et al. Protein phosphatase 2Calpha expression in normal human tissues: an immunohistochemical study. Histochem Cell Biol. 2001;116:31-9 pubmed
    Protein phosphatase (PP2Calpha) is a member of the mammalian serine threonine-specific protein phosphatases family...
  3. Bu S, Kapanadze B, Hsu T, Trojanowska M. Opposite effects of dihydrosphingosine 1-phosphate and sphingosine 1-phosphate on transforming growth factor-beta/Smad signaling are mediated through the PTEN/PPM1A-dependent pathway. J Biol Chem. 2008;283:19593-602 pubmed publisher
    ..We demonstrate a novel function of nuclear PTEN as a co-factor of the Smad2/3 phosphatase, PPM1A. Complex formation of PTEN with PPM1A does not require the lipid phosphatase activity but depends on ..
  4. Sun W, Yu Y, Dotti G, Shen T, Tan X, Savoldo B, et al. PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation. Cell Signal. 2009;21:95-102 pubmed publisher
    ..Using a functional genomic approach, we have identified two protein serine/threonine phosphatases, PPM1A and PPM1B, as IKKbeta phosphatases...
  5. Dai F, Shen T, Li Z, Lin X, Feng X. PPM1A dephosphorylates RanBP3 to enable efficient nuclear export of Smad2 and Smad3. EMBO Rep. 2011;12:1175-81 pubmed publisher
    ..Here we report that protein phosphatase PPM1A regulates the nuclear export of Smad2/3 through targeting nuclear exporter RanBP3...
  6. Das A, Helps N, Cohen P, Barford D. Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution. EMBO J. 1996;15:6798-809 pubmed
  7. Bourgeois B, Gilquin B, Tellier Lebegue C, Ostlund C, Wu W, Perez J, et al. Inhibition of TGF-? signaling at the nuclear envelope: characterization of interactions between MAN1, Smad2 and Smad3, and PPM1A. Sci Signal. 2013;6:ra49 pubmed publisher
    ..of Smad2 and Smad3, thus hindering their recognition by Smad4, and MAN1 bound directly in vitro to the phosphatase PPM1A, which catalyzes the dephosphorylation of Smad2/3...
  8. Lu X, An H, Jin R, Zou M, Guo Y, Su P, et al. PPM1A is a RelA phosphatase with tumor suppressor-like activity. Oncogene. 2014;33:2918-27 pubmed publisher
    ..tumor inhibitory and RelA phosphatase activities of the protein phosphatase 2C (PP2C) phosphatase family member, PPM1A. We show that PPM1A directly dephosphorylated RelA at residues S536 and S276 and selectively inhibited NF-?B ..
  9. Zhang B, Zhou Z, Lin H, Lv X, Fu J, Lin P, et al. Protein phosphatase 1A (PPM1A) is involved in human cytotrophoblast cell invasion and migration. Histochem Cell Biol. 2009;132:169-79 pubmed publisher
    ..Excessive trophoblast invasion leads to hydatidiform moles and choriocarcinoma. PPM1A is a phosphatase which dephosphorylates and inactivates a broad range of substrates, including TGF-beta, MAP ..

More Information


  1. Wang Y, Dow E, Liang Y, Ramakrishnan R, Liu H, Sung T, et al. Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop. J Biol Chem. 2008;283:33578-84 pubmed publisher
    ..Overexpression of PPM1A and the related PPM1B greatly reduced Cdk9 T-loop phosphorylation in vivo...
  2. Yoshizaki T, Maegawa H, Egawa K, Ugi S, Nishio Y, Imamura T, et al. Protein phosphatase-2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. J Biol Chem. 2004;279:22715-26 pubmed
    During differentiation, expression of protein phosphatase-2Calpha (PP2Calpha) is increased in 3T3-L1 adipocytes...
  3. Lin X, Duan X, Liang Y, Su Y, Wrighton K, Long J, et al. PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell. 2006;125:915-28 pubmed
    ..Using a functional genomic approach, we have identified PPM1A/PP2Calpha as a bona fide Smad phosphatase. PPM1A dephosphorylates and promotes nuclear export of TGFbeta-activated Smad2/3...
  4. Zhang S, Wan X, Zhou C, Lu W, Xie X. [Expression and significance of LMP2 and PPM1A in gestational trophoblastic disease]. Zhonghua Fu Chan Ke Za Zhi. 2011;46:510-5 pubmed
    To investigate the expression of low molecular mass polypeptide-2 (LMP2) and protein phosphatase 1A (PPM1A) in gestational trophoblastic disease and elucidate their predictive value in malignant transformation of hydatidiform mole...
  5. Wu S, Wang B, Yang Y, Feng X, Zhao X, Yang D. Expression of PTEN, PPM1A and P-Smad2 in hepatocellular carcinomas and adjacent liver tissues. World J Gastroenterol. 2007;13:4554-9 pubmed
    To investigate the expressions of PTEN, PPM1A and P-Smad2 in hepatocellular carcinoma (HCC) and their significance...
  6. Andryka Dudek P, Ciacka K, Wisniewska A, Bogatek R, Gniazdowska A. Nitric Oxide-Induced Dormancy Removal of Apple Embryos Is Linked to Alterations in Expression of Genes Encoding ABA and JA Biosynthetic or Transduction Pathways and RNA Nitration. Int J Mol Sci. 2019;20: pubmed publisher
    ..and elements of the ABA transduction pathway (PYL1, PYL2, RCAR1, RCAR3, PP2CA, ABI1, ABI2, SNRK2, ABI5, AREB3, ABF)...
  7. Shimizu E, Koshino H, Noro A, Maruyama M, Shimoda N, Uesugi S, et al. Isolation of a spirolactone norditerpenoid as a yeast Ca2+ signal transduction inhibitor from Kuji amber and evaluation of its effects on PPM1A activity. Fitoterapia. 2019;: pubmed publisher
    ..or indirect inhibition of calcineurin activity [protein phosphatase, Mg2+/Mn2+-dependent 1A (PPM1A) activation]...
  8. Chuderland D, Dvashi Z, Kaplan Kraicer R, Ben Meir D, Shalgi R, Lavi S. De novo synthesis of protein phosphatase 1A, magnesium dependent, alpha isoform (PPM1A) during oocyte maturation. Cell Mol Biol Lett. 2012;17:433-45 pubmed publisher
    ..b>Protein phosphatase 1A, magnesium dependent, alpha isoform (PPM1A), which belongs to the metal-dependent serine/threonine protein ..
  9. Yang J, Zhang J, Xu T, Wang Y, Wang Z. [Establishment of BV2 cell line with steady knockdown of Mg2+/Mn2+-dependent protein phosphatase 1A(PPM1A)]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2018;34:818-823 pubmed
    Objective To construct a short hairpin RNA (shRNA) lentiviral of Mg2+/Mn2+-dependent protein phosphatase 1A (PPM1A) gene and establish mouse brain microglia cell line(BV2) which PPM1A was knocked down stably...
  10. Tang J, Gifford C, Samarakoon R, Higgins P. Deregulation of Negative Controls on TGF-?1 Signaling in Tumor Progression. Cancers (Basel). 2018;10: pubmed publisher
    ..Such negative regulators include phosphatase and tensin homologue (PTEN), protein phosphatase magnesium 1A (PPM1A), Klotho, bone morphogenic protein 7 (BMP7), SMAD7, Sloan-Kettering Institute proto-oncogene/ Ski related novel ..
  11. Li W, Wang L, Sheng X, Yan C, Zhou R, Hang J, et al. Molecular basis for the selective and ABA-independent inhibition of PP2CA by PYL13. Cell Res. 2013;23:1369-79 pubmed publisher
    ..Here, we show that PYL13 selectively inhibits the phosphatase activity of PP2CA independent of ABA. The crystal structure of PYL13-PP2CA complex, which was determined at 2...
  12. Schaaf K, Smith S, Duverger A, Wagner F, Wolschendorf F, Westfall A, et al. Mycobacterium tuberculosis exploits the PPM1A signaling pathway to block host macrophage apoptosis. Sci Rep. 2017;7:42101 pubmed publisher
    ..We recently described that Mtb infection upregulated expression of the host phosphatase PPM1A, which impairs the antibacterial response of macrophages...
  13. Lu J, Zhong Y, Chen J, Lin X, Lin Z, Wang N, et al. Radiation Enhances the Epithelial- Mesenchymal Transition of A549 Cells via miR3591-5p/USP33/PPM1A. Cell Physiol Biochem. 2018;50:721-733 pubmed publisher
    ..USP33 could deubiquitinate PPM1A (protein phosphatase, Mg2+/Mn2 + dependent 1A), a phosphatase for Smad2/3...
  14. Duan S, Wang Y, Wang H, Wang S, Ji L, Dai D, et al. A novel PCR-based approach to discover miRNA target genes. Int J Med Sci. 2014;11:1270-4 pubmed publisher
    ..Moreover, our results include 2 genes (SOD2 and PPM1A) that have already been verified as targets of hsa-miR-377...
  15. Hayashi R, Tanoue K, Durell S, Chatterjee D, Jenkins L, Appella D, et al. Optimization of a cyclic peptide inhibitor of Ser/Thr phosphatase PPM1D (Wip1). Biochemistry. 2011;50:4537-49 pubmed publisher
    ..We further developed an inhibitor selective for PPM1D over PPM1A with a K(i) of 2.9 μM...
  16. Sechet J, Roux C, Plessis A, Effroy D, Frey A, Perreau F, et al. The ABA-deficiency suppressor locus HAS2 encodes the PPR protein LOI1/MEF11 involved in mitochondrial RNA editing. Mol Plant. 2015;8:644-56 pubmed publisher
    ..has2/mef11 mutants exhibited phenotypes very similar to the ABA-hypersensitive mutant, hai1-1 pp2ca-1 hab1-1 abi1-2, which is impaired in four genes encoding type 2C protein phosphatases (PP2C) that act as upstream ..
  17. Islam S, Ahmed M, Lee S, Shehzad A, Sonn J, Kwon O, et al. PRP4 kinase induces actin rearrangement and epithelial-mesenchymal transition through modulation of the actin-binding protein cofilin. Exp Cell Res. 2018;369:158-165 pubmed publisher
    ..time-of-flight mass-spectrometry (MALDI-TOF MS) analysis indicated increased expression of protein phosphatase 1A (PP1A) in PRP4-transfected HCT116 cells...
  18. Rizvi F, Siddiqui R, DeFranco A, Homar P, Emelyanova L, Holmuhamedov E, et al. Simvastatin reduces TGF-β1-induced SMAD2/3-dependent human ventricular fibroblasts differentiation: Role of protein phosphatase activation. Int J Cardiol. 2018;270:228-236 pubmed publisher
    ..SMAD2/3 phosphorylation and nuclear translocation, mediated through catalytic activation of protein-phosphatases PPM1A and PP2A, which physically interact with SMAD2/3, thereby promoting their dephosphorylation...
  19. Zhu F, Xie N, Jiang Z, Li G, Ma L, Tong T. The Cellular Senescence-Inhibited Gene Is Essential for PPM1A Myristoylation To Modulate Transforming Growth Factor β Signaling. Mol Cell Biol. 2018;38: pubmed publisher
    ..Our work showed that CSIG is involved in the myristoylation of the serine/threonine protein phosphatase PPM1A. Previous research has shown that myristoylation is necessary for PPM1A to dephosphorylate Smad2 and Smad3...
  20. Pereira J, Chevalier C, Chaze T, Gianetto Q, Impens F, Matondo M, et al. Infection Reveals a Modification of SIRT2 Critical for Chromatin Association. Cell Rep. 2018;23:1124-1137 pubmed publisher
    ..Furthermore, we identify a nuclear complex formed by the phosphatases PPM1A and PPM1B, with SIRT2 essential for controlling H3K18 deacetylation and SIRT2-mediated gene repression during ..
  21. Debnath S, Kosek D, Tagad H, Durell S, Appella D, Acevedo R, et al. A trapped human PPM1A-phosphopeptide complex reveals structural features critical for regulation of PPM protein phosphatase activity. J Biol Chem. 2018;293:7993-8008 pubmed publisher
    ..of Mg2+ or Mn2+ ions for activity in vitro The crystal structure of human PPM1A (also known as PP2Cα), the first PPM structure determined, displays two tightly bound Mn2+ ions in the ..
  22. Shukla A, Edwards R, Yang Y, Hahn A, Folkers K, Ding J, et al. CLIC4 regulates TGF-β-dependent myofibroblast differentiation to produce a cancer stroma. Oncogene. 2014;33:842-50 pubmed publisher
    ..This requirement involves the interaction of CLIC4 with PPM1a, the selective phosphatase of activated p38...
  23. Zhu Y, Ni T, Deng W, Lin J, Zheng L, Zhang C, et al. Effects of NLRP6 on the proliferation and activation of human hepatic stellate cells. Exp Cell Res. 2018;370:383-388 pubmed publisher
    ..phosphorylation of Smad2/3 (p-Smad2/3) and enhanced the expression of protein phosphatase magnesium dependent 1?A (PPM1A), the only phosphatase for Smad2/3...
  24. Han W, Hu P, Wu F, Wang S, Hu Y, Li S, et al. FHL3 links cell growth and self-renewal by modulating SOX4 in glioma. Cell Death Differ. 2019;26:796-811 pubmed publisher
    ..with the Smad2/3 protein complex at the SOX4 promoter region, inhibits SOX4 transcriptional activity by recruiting PPM1A phosphatase to Smad2/3, and then suppresses GSC tumor sphere formation and self-renewal in vitro and in vivo via ..
  25. Zhang Y, Tao R, Wu S, Xu C, Wang J, Chen J, et al. TRIM52 up-regulation in hepatocellular carcinoma cells promotes proliferation, migration and invasion through the ubiquitination of PPM1A. J Exp Clin Cancer Res. 2018;37:116 pubmed publisher
    ..TRIM52, p21, matrix metalloproteinase 2 (MMP2), protein phosphatase, Mg2+/Mn2+ dependent 1A (PPM1A), p-Smad2/3 and Smad2/3 levels in HCC tissues and cell lines...
  26. Dong K, Guo X, Chen W, Hsu A, Shao Q, Chen J, et al. Mesenchyme homeobox 1 mediates transforming growth factor-β (TGF-β)-induced smooth muscle cell differentiation from mouse mesenchymal progenitors. J Biol Chem. 2018;293:8712-8719 pubmed publisher
    ..of TGF-β stimulation because Meox1 inhibited protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) and thereby prevented PPM1A-mediated Smad3 dephosphorylation...
  27. Pan C, Tang J, Xu Y, Xiao P, Liu H, Wang H, et al. The catalytic role of the M2 metal ion in PP2Cα. Sci Rep. 2015;5:8560 pubmed publisher
    ..In this study, we discovered that mutations in the structurally buried D38 residue of PP2Cα (PPM1A) redefined the water-mediated hydrogen network in the active site and selectively disrupted M2 metal ion binding...
  28. Dvashi Z, Sar Shalom H, Shohat M, Ben Meir D, Ferber S, Satchi Fainaro R, et al. Protein phosphatase magnesium dependent 1A governs the wound healing-inflammation-angiogenesis cross talk on injury. Am J Pathol. 2014;184:2936-50 pubmed publisher
    Protein phosphatase magnesium dependent 1A (PPM1A) has been implicated in fibrosis and skin wounding. We generated PPM1A knockout mice to study the role of PPM1A in the wound healing-inflammation-angiogenesis cross talk...
  29. Wu Q, Zhang X, Peirats Llobet M, Belda Palazon B, Wang X, Cui S, et al. Ubiquitin Ligases RGLG1 and RGLG5 Regulate Abscisic Acid Signaling by Controlling the Turnover of Phosphatase PP2CA. Plant Cell. 2016;28:2178-2196 pubmed publisher
    ..We report that RGLG5, together with RGLG1, releases the PP2C blockade of ABA signaling by mediating PP2CA protein degradation...
  30. Shang X, Wang J, Luo Z, Wang Y, Morandi M, Marymont J, et al. Notch signaling indirectly promotes chondrocyte hypertrophy via regulation of BMP signaling and cell cycle arrest. Sci Rep. 2016;6:25594 pubmed publisher
    ..and Western blot results revealed a significant reduction in the expression of the SMAD-related phosphatase, PPM1A, following NICD over-expression...
  31. Huang K, Lin W, Cheng W. Salt hypersensitive mutant 9, a nucleolar APUM23 protein, is essential for salt sensitivity in association with the ABA signaling pathway in Arabidopsis. BMC Plant Biol. 2018;18:40 pubmed publisher
    ..Importantly, NCED3, ABI2, PP2CA, and major ABA-responsive marker genes, such as RD20 and RD29B, were down-regulated at both the transcript and ..
  32. Coates R, Gardner J, Gao Y, Cortright V, Mitchell J, Ashikaga T, et al. Significance of positive and inhibitory regulators in the TGF-? signaling pathway in colorectal cancers. Hum Pathol. 2017;66:34-39 pubmed publisher
    ..High levels of serum TGF-?1 were reported in patients with CRC and were associated with poor clinical outcome. PPM1A is an important inhibitory regulator in the TGF-? signaling pathway and contributes to terminating the TGF-?/SMAD ..
  33. Mummidi S, Das N, Carpenter A, Kandikattu H, Krenz M, Siebenlist U, et al. Metformin inhibits aldosterone-induced cardiac fibroblast activation, migration and proliferation in vitro, and reverses aldosterone+salt-induced cardiac fibrosis in vivo. J Mol Cell Cardiol. 2016;98:95-102 pubmed publisher
    ..Further, Aldo induced PPM1A (Protein Phosphatase Magnesium Dependent 1A) activation and inhibited AMPK phosphorylation...
  34. Chen J, Yu F, Liu Y, Du C, Li X, Zhu S, et al. FERONIA interacts with ABI2-type phosphatases to facilitate signaling cross-talk between abscisic acid and RALF peptide in Arabidopsis. Proc Natl Acad Sci U S A. 2016;113:E5519-27 pubmed publisher
    ..RESISTANCE (PYR)/PYR1-LIKE (PYL)/REGULATORY COMPONENTS OF ABA RECEPTORS (RCAR)-A-type protein phosphatase type 2C (PP2CA) modules...
  35. Krzywinska E, Kulik A, Bucholc M, Fernandez M, Rodriguez P, Dobrowolska G. Protein phosphatase type 2C PP2CA together with ABI1 inhibits SnRK2.4 activity and regulates plant responses to salinity. Plant Signal Behav. 2016;11:e1253647 pubmed publisher
    ..4, a kinase not activated in response to ABA. Here, we show that another member of this clade - PP2CA, interacts with and inhibits SnRK2.4. The salt-induced SnRK2.4/SnRK2...
  36. Bhatnagar N, Min M, Choi E, Kim N, Moon S, Yoon I, et al. The protein phosphatase 2C clade A protein OsPP2C51 positively regulates seed germination by directly inactivating OsbZIP10. Plant Mol Biol. 2017;93:389-401 pubmed publisher
    ..To elucidate the role of PP2CA genes in germination of rice seed, we selected OsPP2C51, which shows highly specific expression in the embryo ..
  37. Sugiyama Y, Yamashita S, Uezato Y, Senga Y, Katayama S, Goshima N, et al. Phosphorylated TandeMBP: A unique protein substrate for protein phosphatase assay. Anal Biochem. 2016;513:47-53 pubmed publisher
    ..Moreover, P-TandeMBP served as an efficient substrate for PPM family phosphatases (PPM1A, PPM1B, PPM1D, PPM1F, PPM1G, PPM1H, PPM1K, and PPM1M) and PPP family phosphatase PP5...
  38. Peirats Llobet M, Han S, Gonzalez Guzman M, Jeong C, Rodriguez L, Belda Palazon B, et al. A Direct Link between Abscisic Acid Sensing and the Chromatin-Remodeling ATPase BRAHMA via Core ABA Signaling Pathway Components. Mol Plant. 2016;9:136-147 pubmed publisher
    ..Our data suggest that SnRK2-dependent phosphorylation of BRM leads to its inhibition, and PP2CA-mediated dephosphorylation of BRM restores the ability of BRM to repress ABA response...
  39. Li Z, Waadt R, Schroeder J. Release of GTP Exchange Factor Mediated Down-Regulation of Abscisic Acid Signal Transduction through ABA-Induced Rapid Degradation of RopGEFs. PLoS Biol. 2016;14:e1002461 pubmed publisher
    ..Interestingly, RopGEF1 undergoes constitutive degradation in pp2c quadruple abi1/abi2/hab1/pp2ca mutant plants, revealing that active PP2C protein phosphatases protect and stabilize RopGEF1 from ABA-mediated ..
  40. Smith S, Schaaf K, Rajabalee N, Wagner F, Duverger A, Kutsch O, et al. The phosphatase PPM1A controls monocyte-to-macrophage differentiation. Sci Rep. 2018;8:902 pubmed publisher
    ..differentiation is controlled by the Protein Phosphatase, Mg2+/Mn2+-dependent 1A (PPM1A)...
  41. Krieglstein J, Kewitz T, Kirchhefer U, Hofnagel O, Weissen Plenz G, Reinbold M, et al. Damage of guinea pig heart and arteries by a trioleate-enriched diet and of cultured cardiomyocytes by oleic acid. PLoS ONE. 2010;5:e9561 pubmed publisher
    ..The apoptotic effect caused by oleic acid was diminished when PP2C alpha and beta were downregulated by siRNA showing that PP2C was causally involved in apoptosis caused by oleic acid...
  42. Woolbright B, Williams C, Ni H, Kumer S, Schmitt T, Kane B, et al. Microcystin-LR induced liver injury in mice and in primary human hepatocytes is caused by oncotic necrosis. Toxicon. 2017;125:99-109 pubmed publisher
    ..arginine (MC-LR) by organic anion transporting polypeptide 1B2 in hepatocytes results in inhibition of protein phosphatase 1A and 2A, and subsequent cell death...
  43. Xin Y, Wang D, Huang M, Yu J, Fang L, Xiao S. Proteome analysis of differential protein expression in porcine alveolar macrophages regulated by porcine reproductive and respiratory syndrome virus nsp1? protein. Virus Genes. 2018;54:385-396 pubmed publisher
    ..of outer membrane complex 70 (TOM70), involved in type I IFN induction, were downregulated, while protein phosphatase 1A (PPM1A), related to the inhibition of NF-?B pathway activation, was upregulated in nsp1?-overexpressed PAM ..
  44. Lyu P, Zhang S, Yuen H, McCrudden C, Wen Q, Chan K, et al. Identification of TWIST-interacting genes in prostate cancer. Sci China Life Sci. 2017;60:386-396 pubmed publisher
    ..cohort and a prostate cancer cell line dataset, we have identified three potential downstream targets of TWIST, PPM1A, SRP72 and TBCB. TWIST's prognostic capacity is lost when the gene is mutated...
  45. Xiang W, Zhang Q, Lin X, Wu S, Zhou Y, Meng F, et al. PPM1A silences cytosolic RNA sensing and antiviral defense through direct dephosphorylation of MAVS and TBK1. Sci Adv. 2016;2:e1501889 pubmed publisher
    ..We reported that protein phosphatase magnesium-dependent 1A (PPM1A; also known as PP2C?), depending on its catalytic ability, dampened the RLR-IRF3 (interferon regulatory factor 3) ..
  46. Brautigan D. Protein Ser/Thr phosphatases--the ugly ducklings of cell signalling. FEBS J. 2013;280:324-45 pubmed publisher
    ..Signalling networks and modelling schemes need to incorporate the full gamut of protein Ser/Thr phosphatases and their interconnections. ..
  47. Cheng A, Ross K, Kaldis P, Solomon M. Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases. Genes Dev. 1999;13:2946-57 pubmed
    ..Furthermore, PP2C-like enzymes are the predominant phosphatases toward human Cdk2 in HeLa cell extracts, indicating that the substrate specificity of PP2Cs toward CDKs is evolutionarily conserved. ..
  48. Zhou Y, Zhao Y, Gao Y, Hu W, Qu Y, Lou N, et al. Hepatitis C virus NS3 protein enhances hepatocellular carcinoma cell invasion by promoting PPM1A ubiquitination and degradation. J Exp Clin Cancer Res. 2017;36:42 pubmed publisher
    ..Protein phosphatase magnesium-dependent 1A (PPM1A) has recently emerged as an important tumor suppressor as it can block a range of tumor-centric signaling pathways ..
  49. Xiao K, McClatchy D, Shukla A, Zhao Y, Chen M, Shenoy S, et al. Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proc Natl Acad Sci U S A. 2007;104:12011-6 pubmed
    ..This study provides a comprehensive analysis of proteins that bind beta-arrestin isoforms and underscores their potentially broad regulatory roles in mammalian cellular physiology. ..
  50. Srivastava J, Goris J, Dilworth S, Parker P. Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by nucleotides. FEBS Lett. 2002;516:265-9 pubmed
    The protein phosphatases PP1(c), PP2A(c) and PP2Calpha are shown to dephosphorylate protein kinase Cdelta (PKCdelta) in vitro; of these PP2A(c) displayed the highest specific activity towards PKCdelta...
  51. Strovel E, Wu D, Sussman D. Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription. J Biol Chem. 2000;275:2399-403 pubmed
    ..PP2C utilizes Axin as a substrate both in vitro and in vivo and decreases its half-life. These results indicate that PP2C is a positive regulator of Wnt signal transduction and mediates its effects through the dephosphorylation of Axin. ..
  52. Chau J, Jia D, Wang Z, Liu Z, Hu Y, Zhang X, et al. A crucial role for bone morphogenetic protein-Smad1 signalling in the DNA damage response. Nat Commun. 2012;3:836 pubmed publisher
    ..BMPs-activated Smad1 in the nucleus on S239, which disrupts Smad1 interaction with protein phosphatase PPM1A, leading to enhanced activation and upregulation of Smad1...
  53. Hishiya A, Ohnishi M, Tamura S, Nakamura F. Protein phosphatase 2C inactivates F-actin binding of human platelet moesin. J Biol Chem. 1999;274:26705-12 pubmed
    ..The purified enzyme, as well as bacterially made PP2Calpha and PP2Cbeta, efficiently dephosphorylate(s) highly purified platelet phospho-moesin...
  54. Liu Y, Xu Y, Ma H, Wang B, Xu L, Zhang H, et al. Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a. Oncotarget. 2016;7:33125-35 pubmed publisher
    ..Protein phosphatase magnesium dependent 1A (PPM1a) functions as a phosphatase essential for terminating the TGF-β signaling pathway by dephosphorylating p-Smad2/..
  55. Sun J, Schaaf K, Duverger A, Wolschendorf F, Speer A, Wagner F, et al. Protein phosphatase, Mg2+/Mn2+-dependent 1A controls the innate antiviral and antibacterial response of macrophages during HIV-1 and Mycobacterium tuberculosis infection. Oncotarget. 2016;7:15394-409 pubmed publisher
    ..We here identify Protein Phosphatase, Mg2+/Mn2+-dependent 1A (PPM1A) as a molecular link between Mtb infection and increased HIV-1 susceptibility of macrophages...
  56. Li Z, Liu G, Sun L, Teng Y, Guo X, Jia J, et al. PPM1A regulates antiviral signaling by antagonizing TBK1-mediated STING phosphorylation and aggregation. PLoS Pathog. 2015;11:e1004783 pubmed publisher
    ..However, the molecular mechanism underlying the regulation of STING remains unclear. Here, we show that PPM1A negatively regulates antiviral signaling by targeting STING in its phosphatase activity-dependent manner, and in a ..
  57. Samarakoon R, Rehfuss A, Khakoo N, Falke L, Dobberfuhl A, Helo S, et al. Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair. FASEB J. 2016;30:3308-3320 pubmed
    Protein phosphatase magnesium-dependent-1A (PPM1A) dephosphorylates SMAD2/3, which suppresses TGF-? signaling in keratinocytes and during Xenopus development; however, potential involvement of PPM1A in chronic kidney disease is unknown...
  58. Li R, Gong Z, Pan C, Xie D, Tang J, Cui M, et al. Metal-dependent protein phosphatase 1A functions as an extracellular signal-regulated kinase phosphatase. FEBS J. 2013;280:2700-11 pubmed publisher
    ..In this study, we found that PPM1A negatively regulated ERK by directly dephosphorylating its pThr202 position early in EGF stimulation...
  59. Ramasamy A, Curjuric I, Coin L, Kumar A, McArdle W, Imboden M, et al. A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. J Allergy Clin Immunol. 2011;128:996-1005 pubmed publisher
    ..This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses. ..
  60. Giagulli C, D Ursi P, He W, Zorzan S, Caccuri F, Varney K, et al. A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Sci Rep. 2017;7:6555 pubmed publisher
    ..Our findings offer new opportunities to understand the molecular mechanisms accounting for the B-cell growth-promoting activity of vp17s. ..
  61. Gallego Fabrega C, Carrera C, Reny J, Fontana P, Slowik A, Pera J, et al. PPM1A Methylation Is Associated With Vascular Recurrence in Aspirin-Treated Patients. Stroke. 2016;47:1926-9 pubmed publisher
    ..69×10(-06), RAF1), cg04985020 (P=3.47×10(-03), PPM1A), and cg08419850 (P=3.47×10(-03), KCNQ1)...
  62. Budhiraja S, Ramakrishnan R, Rice A. Phosphatase PPM1A negatively regulates P-TEFb function in resting CD4(+) T cells and inhibits HIV-1 gene expression. Retrovirology. 2012;9:52 pubmed publisher
    ..We investigated the role of phosphatase PPM1A in regulating CDK9 T-loop phosphorylation and its effect on HIV-1 proviral transcription...
  63. Flajolet M, Rakhilin S, Wang H, Starkova N, Nuangchamnong N, Nairn A, et al. Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3. Proc Natl Acad Sci U S A. 2003;100:16006-11 pubmed
    ..that the 50-aa C-terminal cytoplasmic tail of mGluR3 interacts specifically with protein phosphatase 2Calpha (PP2Calpha). This interaction was confirmed by GST pull-down and coimmunoprecipitation assays...
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    ..Therefore, here we report a detailed biochemical study to elucidate the kinetic and chemical mechanism of PP2Calpha. Steady-state kinetic and product inhibition studies revealed that PP2Calpha employs an ordered sequential ..
  65. Fan J, Yang M, Ouyang Q, Fu D, Xu Z, Liu X, et al. Phosphatase PPM1A is a novel prognostic marker in pancreatic ductal adenocarcinoma. Hum Pathol. 2016;55:151-8 pubmed publisher
    ..Investigating additional prognostic markers is warranted. PPM1A is a phosphatase that dephosphorylates TGF-?-activated Smad2/3 and inactivates the TGF-? signaling...
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    ..phosphatase activity of Ppm1E and Ppm1F, but not that attributable to other PPM family members, including Ppm1A/PP2C?...
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    ..Thus, we have revealed a conserved mechanism of centromeric protection of eukaryotic chromosomes in mitosis and meiosis. ..
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    ..During our yeast two-hybrid screening, PP2calpha was pulled out by both N- and P/Q-type Ca2+ channel C termini...
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    ..These observations suggest that the binding of Mg2+ to the D146/D239 binding site stabilizes the conformation of the active site and the Flap subdomain. ..
  70. Ofek P, Ben Meir D, Kariv Inbal Z, Oren M, Lavi S. Cell cycle regulation and p53 activation by protein phosphatase 2C alpha. J Biol Chem. 2003;278:14299-305 pubmed
    ..We now demonstrate that PP2C alpha, a major mammalian isoform, inhibits cell growth and activates the p53 pathway...
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    ..These findings are discussed in terms of current knowledge of the specificity of these two protein phosphatases. ..
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    ..In this study, we have found that PPM1A, a metal ion-dependent protein serine/threonine phosphatase, physically interacts with and dephosphorylates Smad1 ..
  74. Malki K, Uher R, Paya Cano J, Binder E, Rietschel M, Zobel A, et al. Convergent animal and human evidence suggests a role of PPM1A gene in response to antidepressants. Biol Psychiatry. 2011;69:360-5 pubmed publisher
    ..Several polymorphisms in the protein phosphatase 1A gene (PPM1A) remained significantly associated with response to nortriptyline in humans after correction ..
  75. Tan K, Chan S, Tan K, Yu V. The Caenorhabditis elegans sex-determining protein FEM-2 and its human homologue, hFEM-2, are Ca2+/calmodulin-dependent protein kinase phosphatases that promote apoptosis. J Biol Chem. 2001;276:44193-202 pubmed
    ..hFEM-2 and FEM-2, but not PP2Calpha, were demonstrated to dephosphorylate CaM kinase II efficiently in vitro, suggesting that hFEM-2 and FEM-2 are ..
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    Fractionation of brain extracts and functional biochemical assays identified PP2Calpha, a serine/threonine phosphatase, as the major biochemical activity inhibiting PAK1...
  77. Wang J, Tucker Kellogg L, Ng I, Jia R, Thiagarajan P, White J, et al. The self-limiting dynamics of TGF-? signaling in silico and in vitro, with negative feedback through PPM1A upregulation. PLoS Comput Biol. 2014;10:e1003573 pubmed publisher
    ..We then proposed a negative feedback loop with upregulation of the phosphatase PPM1A. The resulting model was able to explain the dynamics of Smad signaling, under both short and long exposures to ..
  78. Tanoue K, Miller Jenkins L, Durell S, Debnath S, Sakai H, Tagad H, et al. Binding of a third metal ion by the human phosphatases PP2Cα and Wip1 is required for phosphatase activity. Biochemistry. 2013;52:5830-43 pubmed publisher
    ..The human phosphatases PP2Cα (PPM1A) and Wip1 (PPM1D) differ in their physiological function, substrate specificity, and apparent metal affinity...
  79. Geng J, Fan J, Ouyang Q, Zhang X, Zhang X, Yu J, et al. Loss of PPM1A expression enhances invasion and the epithelial-to-mesenchymal transition in bladder cancer by activating the TGF-?/Smad signaling pathway. Oncotarget. 2014;5:5700-11 pubmed
    ..Protein phosphatase PPM1A has been reported to dephosphorylate TGF-?-activated Smad2/3, thus inhibiting the TGF-? signaling pathway...