Gene Symbol: Ppp1ca
Description: protein phosphatase 1, catalytic subunit, alpha isoform
Alias: Ppp1c, dism2, serine/threonine-protein phosphatase PP1-alpha catalytic subunit, PP-1A
Species: mouse
Products:     Ppp1ca

Top Publications

  1. Lee H, Chen R, Kim H, Etchegaray J, Weaver D, Lee C. The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1. Proc Natl Acad Sci U S A. 2011;108:16451-6 pubmed publisher
    ..Thus, our findings provide clear insights into the molecular basis of how the period and phase of our daily rhythms are determined. ..
  2. Nawa M, Kanekura K, Hashimoto Y, Aiso S, Matsuoka M. A novel Akt/PKB-interacting protein promotes cell adhesion and inhibits familial amyotrophic lateral sclerosis-linked mutant SOD1-induced neuronal death via inhibition of PP2A-mediated dephosphorylation of Akt/PKB. Cell Signal. 2008;20:493-505 pubmed
    ..Given its ubiquitous expression, BTBD10 appears to behave as a suppressor of cell death including neuronal cell death related to ALS and an enhancer of cell growth via its positive regulation of Akt phosphorylation. ..
  3. Gallego M, Kang H, Virshup D. Protein phosphatase 1 regulates the stability of the circadian protein PER2. Biochem J. 2006;399:169-75 pubmed publisher
    ..Over-expression of the PP1 inhibitors, protein phosphatase 1 holoenzyme inhibitor-1 and Inhibitor-2, confirmed these results. Thus PP1 regulates PER2 stability and is therefore a candidate to regulate mammalian circadian rhythms...
  4. Schmutz I, Wendt S, Schnell A, Kramer A, Mansuy I, Albrecht U. Protein phosphatase 1 (PP1) is a post-translational regulator of the mammalian circadian clock. PLoS ONE. 2011;6:e21325 pubmed publisher
    ..Hence, PP1, may reduce PER2 phosphorylation thereby influencing nuclear localization of this protein. This may at least partially influence period and phase shifting properties of the mammalian circadian clock. ..
  5. Ha N, Tonozuka T, Stamos J, Choi H, Weis W. Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation. Mol Cell. 2004;15:511-21 pubmed
    ..Phosphorylated APC and axin bind to the same surface of, and compete directly for, beta-catenin. The structural and biochemical data suggest a novel model for how APC functions in beta-catenin degradation. ..
  6. Fleischer A, Ghadiri A, Dessauge F, Duhamel M, Cayla X, Garcia A, et al. Bad-dependent rafts alteration is a consequence of an early intracellular signal triggered by interleukin-4 deprivation. Mol Cancer Res. 2004;2:674-84 pubmed
  7. Jiang Y, Luo W, Howe P. Dab2 stabilizes Axin and attenuates Wnt/beta-catenin signaling by preventing protein phosphatase 1 (PP1)-Axin interactions. Oncogene. 2009;28:2999-3007 pubmed publisher
    ..We conclude that Dab2 stabilizes Axin and attenuates Wnt/beta-catenin signaling by preventing PP1 from binding Axin. ..
  8. Castro M, Ferrer I, Cascon A, Guijarro M, Lleonart M, Ramon Y Cajal S, et al. PPP1CA contributes to the senescence program induced by oncogenic Ras. Carcinogenesis. 2008;29:491-9 pubmed publisher
    ..Applying a retroviral-based genetic screen, we obtained an antisense RNA fragment against PPP1CA, the catalytic subunit of protein phosphatase 1alpha, whose loss of function bypasses ras/p53-induced growth ..
  9. Wallach T, Schellenberg K, Maier B, Kalathur R, Porras P, Wanker E, et al. Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions. PLoS Genet. 2013;9:e1003398 pubmed publisher
    ..Moreover, we predict that circadian PPIs dynamically connect many important cellular processes (signal transduction, cell cycle, etc.) contributing to temporal organization of cellular physiology in an unprecedented manner. ..

Scientific Experts

More Information


  1. Garcia Haro L, Garcia Gimeno M, Neumann D, Beullens M, Bollen M, Sanz P. Glucose-dependent regulation of AMP-activated protein kinase in MIN6 beta cells is not affected by the protein kinase A pathway. FEBS Lett. 2012;586:4241-7 pubmed publisher
    ..Thus, although phosphorylation of Thr172 and Ser485/Ser497 are inversely correlated in response to glucose, they follow an independent regulation. ..
  2. Brüchert N, Mavila N, Boknik P, Baba H, Fabritz L, Gergs U, et al. Inhibitor-2 prevents protein phosphatase 1-induced cardiac hypertrophy and mortality. Am J Physiol Heart Circ Physiol. 2008;295:H1539-46 pubmed publisher
    ..Therefore, PP1 inhibitors such as I-2 could offer new therapeutic options to ameliorate the deleterious effects of heart failure. ..
  3. Traweger A, Wiggin G, Taylor L, Tate S, Metalnikov P, Pawson T. Protein phosphatase 1 regulates the phosphorylation state of the polarity scaffold Par-3. Proc Natl Acad Sci U S A. 2008;105:10402-7 pubmed publisher
  4. Terry Lorenzo R, Carmody L, Voltz J, Connor J, Li S, Smith F, et al. The neuronal actin-binding proteins, neurabin I and neurabin II, recruit specific isoforms of protein phosphatase-1 catalytic subunits. J Biol Chem. 2002;277:27716-24 pubmed
    ..These studies identified some of the structural determinants in PP1 and neurabins that together contribute to preferential targeting of PP1gamma1 and PP1alpha to the mammalian synapse. ..
  5. Fernandes M, Lespinasse F, Rotomondo F, Poirier C, Guenet J, Gaudray P, et al. Comparative mapping of two adjacent regions of MMU19 with their human counterpart on HSA11q13. Cytogenet Cell Genet. 1998;81:237-46 pubmed
    ..5-Mb region. Strikingly, the 0.5-Mb region has a similar size in human but gene order is shuffled. The overall comparative map shows that these two regions are inverted on MMU19 when compared with HSA11q13. ..
  6. Falco G, Stanghellini I, Ko M. Use of Chuk as an internal standard suitable for quantitative RT-PCR in mouse preimplantation embryos. Reprod Biomed Online. 2006;13:394-403 pubmed
    ..It is concluded that Chuk, unlike other commonly used normalization controls, is a reliable and suitable internal standard for measuring gene expression levels by Q-PCR in mouse oocytes and preimplantation embryos. ..
  7. Smith G, Sadhu A, Mathies S, Wolf D. Characterization of protein phosphatases in mouse oocytes. Dev Biol. 1998;204:537-49 pubmed
    ..The differential localization of PP1alpha and PP2A, in addition to the relocation of PP1alpha during the acquisition of meiotic competence, suggests that these PPs have distinct regulatory roles during the resumption of meiosis. ..
  8. Hrabchak C, Varmuza S. Identification of the spermatogenic zip protein Spz1 as a putative protein phosphatase-1 (PP1) regulatory protein that specifically binds the PP1cgamma2 splice variant in mouse testis. J Biol Chem. 2004;279:37079-86 pubmed
    ..We propose that the interaction between Spz1 and PP1cgamma2 may be required for proper regulation of spermatogenesis and fertility in males. ..
  9. Kim T, Goodman J, Anderson K, Niswander L. Phactr4 regulates neural tube and optic fissure closure by controlling PP1-, Rb-, and E2F1-regulated cell-cycle progression. Dev Cell. 2007;13:87-102 pubmed
    ..Thus, Phactr4 is critical for the spatially and temporally regulated transition in proliferation through differential regulation of PP1 and the cell cycle during neurulation and eye development...
  10. Nawa M, Matsuoka M. KCTD20, a relative of BTBD10, is a positive regulator of Akt. BMC Biochem. 2013;14:27 pubmed publisher
    ..KCTD20 was ubiquitously expressed in non-nervous as well as nervous tissues. KCTD20 is a positive regulator of Akt and may play an important role in regulating the death and growth of some non-nervous and nervous cells. ..
  11. Farinelli M, Heitz F, Grewe B, Tyagarajan S, Helmchen F, Mansuy I. Selective regulation of NR2B by protein phosphatase-1 for the control of the NMDA receptor in neuroprotection. PLoS ONE. 2012;7:e34047 pubmed publisher
    ..They provide a new target for the development of potential therapeutic treatment of neurodegeneration. ..
  12. Bose S, Hutson I, Harris C. Hepatic Glucocorticoid Receptor Plays a Greater Role Than Adipose GR in Metabolic Syndrome Despite Renal Compensation. Endocrinology. 2016;157:4943-4960 pubmed
    ..This indicates that liver GR might be more important in development of MS in dexamethasone-treated mice, whereas adipose GR plays a little role in these paradigms. ..
  13. Peters M, Bletsch M, Catapano R, Zhang X, Tully T, Bourtchouladze R. RNA interference in hippocampus demonstrates opposing roles for CREB and PP1alpha in contextual and temporal long-term memory. Genes Brain Behav. 2009;8:320-9 pubmed publisher
    ..More generally, we establish that direct injection of siRNA into identified adult brain regions yields specific gene knockdowns, which can be used to validate in vivo candidate genes involved in behavioral plasticity. ..
  14. Latreille M, Larose L. Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress. J Biol Chem. 2006;281:26633-44 pubmed
    ..In this manner, Nck modulates translation and eIF2alpha signaling in response to ER stress. ..
  15. Braz J, Gregory K, Pathak A, Zhao W, Sahin B, Klevitsky R, et al. PKC-alpha regulates cardiac contractility and propensity toward heart failure. Nat Med. 2004;10:248-54 pubmed
    ..Thus, PKC-alpha functions as a nodal integrator of cardiac contractility by sensing intracellular Ca(2+) and signal transduction events, which can profoundly affect propensity toward heart failure. ..
  16. Ishii J, Adachi H, Shibata N, Arai H, Tsujimoto M. Scavenger receptor expressed by endothelial cells (SREC)-I interacts with protein phosphatase 1alpha in L cells to induce neurite-like outgrowth. Biochem Biophys Res Commun. 2007;360:269-74 pubmed
    ..Our system may be useful for the elucidation of the mechanism of morphological maturation of neuronal cells such as dorsal root ganglion neurons that express SREC-I during early development. ..
  17. Carr A, Schmidt A, Suzuki Y, Del Monte F, Sato Y, Lanner C, et al. Type 1 phosphatase, a negative regulator of cardiac function. Mol Cell Biol. 2002;22:4124-35 pubmed
    ..Thus, PP1 is an important regulator of cardiac function, and inhibition of its activity may represent a novel therapeutic target in heart failure. ..
  18. Ayllon V, Cayla X, Garcia A, Fleischer A, Rebollo A. The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad. Eur J Immunol. 2002;32:1847-55 pubmed
    ..These results suggest that Bcl-xL and Bcl-w are PP1alpha targeting subunits and this trimolecular complex may be involved in the control of apoptosis. ..
  19. Zhang T, Wang S, Lin Y, Xu W, Ye D, Xiong Y, et al. Acetylation negatively regulates glycogen phosphorylase by recruiting protein phosphatase 1. Cell Metab. 2012;15:75-87 pubmed publisher
    ..Our results provide molecular insights into the intricate regulation of the classical GP and a functional crosstalk between protein acetylation and phosphorylation. ..
  20. Lobbestael E, Zhao J, Rudenko I, Beylina A, Gao F, Wetter J, et al. Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle. Biochem J. 2013;456:119-28 pubmed publisher
    ..In conclusion, the present study reveals PP1 as the physiological LRRK2 phosphatase, responsible for LRRK2 dephosphorylation observed in PD mutant LRRK2 and after LRRK2 kinase inhibition. ..
  21. Pradhan S, Khatlani T, Nairn A, Vijayan K. The heterotrimeric G protein G?1 interacts with the catalytic subunit of protein phosphatase 1 and modulates G protein-coupled receptor signaling in platelets. J Biol Chem. 2017;292:13133-13142 pubmed publisher
    ..These findings suggest that G?1 protein enlists PP1c to modulate GPCR signaling in platelets. ..
  22. Kakiya N, Saito T, Nilsson P, Matsuba Y, Tsubuki S, Takei N, et al. Cell surface expression of the major amyloid-? peptide (A?)-degrading enzyme, neprilysin, depends on phosphorylation by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) and dephosphorylation by protein phosphatase 1. J Biol Chem. 2012;287:29362-72 pubmed publisher
  23. Varmuza S, Jurisicova A, Okano K, Hudson J, Boekelheide K, Shipp E. Spermiogenesis is impaired in mice bearing a targeted mutation in the protein phosphatase 1cgamma gene. Dev Biol. 1999;205:98-110 pubmed
    ..These defects are discussed in the light of known functions of protein phosphatase 1. ..
  24. Luo X, Zhang Y, Ruan X, Jiang X, Zhu L, Wang X, et al. Fasting-induced protein phosphatase 1 regulatory subunit contributes to postprandial blood glucose homeostasis via regulation of hepatic glycogenesis. Diabetes. 2011;60:1435-45 pubmed publisher
    ..Because of its unique expression pattern, PPP1R3G plays a major role to control postprandial glucose homeostasis during the fasting-feeding transition via its regulation on liver glycogenesis. ..
  25. Cid C, Garcia Bonilla L, Camafeita E, Burda J, Salinas M, Alcazar A. Proteomic characterization of protein phosphatase 1 complexes in ischemia-reperfusion and ischemic tolerance. Proteomics. 2007;7:3207-18 pubmed
    ..It supports a potential role of PP1 in IR stress and as a target of the endogenous protective mechanisms induced by IT. ..
  26. Vanhalst K, Kools P, Staes K, van Roy F, Redies C. delta-Protocadherins: a gene family expressed differentially in the mouse brain. Cell Mol Life Sci. 2005;62:1247-59 pubmed
    ..Together, these results suggest that the members of the delta1-protocadherin subgroup exercise tightly regulated functions in the development, regionalization, and functional differentiation of the mouse brain. ..
  27. Hormi Carver K, Shi W, Liu C, Berndt N. Protein phosphatase 1alpha is required for murine lung growth and morphogenesis. Dev Dyn. 2004;229:791-801 pubmed
    ..These data suggest that PP1alpha is required for branching morphogenesis and differentiation. ..
  28. Llorian M, Beullens M, Andrés I, Ortiz J, Bollen M. SIPP1, a novel pre-mRNA splicing factor and interactor of protein phosphatase-1. Biochem J. 2004;378:229-38 pubmed
    ..Finally, we found that SIPP1 is also a component of the spliceosomes and that a SIPP1-fragment inhibits splicing catalysis by nuclear extracts independent of its ability to interact with PP1. ..
  29. Zhou T, Li J, Zhao P, Liu H, Jia D, Jia H, et al. Palmitoyl acyltransferase Aph2 in cardiac function and the development of cardiomyopathy. Proc Natl Acad Sci U S A. 2015;112:15666-71 pubmed publisher
    ..These findings establish Aph2 as a critical in vivo regulator of cardiac function and reveal roles for protein palmitoylation in the development of other organs including eyes. ..
  30. Liu W, Li Y, Zhang L, Chen H, Sun S, Liu J, et al. Differential expression of the catalytic subunits for PP-1 and PP-2A and the regulatory subunits for PP-2A in mouse eye. Mol Vis. 2008;14:762-73 pubmed
  31. Yang F, Aiello D, Pyle W. Cardiac myofilament regulation by protein phosphatase type 1alpha and CapZ. Biochem Cell Biol. 2008;86:70-8 pubmed publisher
    ..Our results demonstrate myofilament regulation by PP1alpha and support the concept that cardiac Z-discs are vital components in intracellular signalling. ..
  32. Becker W, Kentrup H, Klumpp S, Schultz J, Joost H. Molecular cloning of a protein serine/threonine phosphatase containing a putative regulatory tetratricopeptide repeat domain. J Biol Chem. 1994;269:22586-92 pubmed
    ..It is suggested that the TPR domain of PPT may be involved in the regulation of the function of this novel protein phosphatase. ..
  33. Saadat M, Kakinoki Y, Mizuno Y, Kikuchi K, Yoshida M. Chromosomal localization of human, rat, and mouse protein phosphatase type 1 beta catalytic subunit genes (PPP1CB) by fluorescence in situ hybridization. Jpn J Genet. 1994;69:697-700 pubmed
  34. Saadat M, Mizuno Y, Kikuchi K, Yoshida M. Comparative mapping of the gene encoding the catalytic subunit of protein phosphatase type 1 alpha (PPP1CA) to human, rat, and mouse chromosomes. Cytogenet Cell Genet. 1995;70:55-7 pubmed
    ..in situ hybridization method, the gene encoding the protein phosphatase type 1 alpha catalytic subunit (PPP1CA) was localized to human chromosome band 11q13, rat chromosome band 1q43, and mouse chromosome band 7E3-F2...
  35. Kissil J, Wilker E, Johnson K, Eckman M, Yaffe M, Jacks T. Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1. Mol Cell. 2003;12:841-9 pubmed
    ..This link provides a possible mechanism for the effect of loss of merlin expression in tumorigenesis...
  36. Wang D, Xue P, Chen X, Xie Z, Yang F, Zheng L, et al. Angiotensin IV upregulates the activity of protein phosphatase 1? in Neura-2A cells. Protein Cell. 2013;4:520-8 pubmed publisher
    ..These changes are consistent with an observed decrease in cell proliferation. Taken together, our study suggests that Ang IV functions via regulating the activity of PP1. ..
  37. Chiang D, Lebesgue N, Beavers D, Alsina K, Damen J, Voigt N, et al. Alterations in the interactome of serine/threonine protein phosphatase type-1 in atrial fibrillation patients. J Am Coll Cardiol. 2015;65:163-73 pubmed publisher
    ..This represents a novel concept in AF pathogenesis and may provide more specific drug targets for treating AF. ..
  38. Nagarajan S, Vohra T, Loffing J, Faresse N. Protein Phosphatase 1α enhances renal aldosterone signaling via mineralocorticoid receptor stabilization. Mol Cell Endocrinol. 2017;450:74-82 pubmed publisher
    ..Thus, our findings describe an original mechanism involving a phosphatase in the regulation of aldosterone signaling and provide new and important insights into the molecular mechanism underlying the MR turnover. ..