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Gene Review

PPP1R12A  -  protein phosphatase 1, regulatory subunit 12A

Homo sapiens

Synonyms: M130, MBS, MYPT1, Myosin phosphatase target subunit 1, Myosin phosphatase-targeting subunit 1, ...
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Disease relevance of PPP1R12A

  • Analysis of the expression and phosphorylation of Ca(2+)-sensitizing proteins (MYPT1 and CPI-17) in vessels from rats and patients with cirrhosis suggested decreased Ca2+ sensitivity [1].
  • This phosphorylation of MYPT1 was significantly inhibited by application of Y-27632 and by pretreatment with pertussis toxin [2].
  • We tested the hypothesis that hypoxia induces Ca(2+)-desensitizing hypoxic relaxation via dephosphorylation of p-MYPT1, consequently increasing MLCP activity and thus decreasing p-MRLC. alpha-Toxin-permeabilized PCASM pretreated with ATPgammaS did not relax in response to hypoxia [3].
  • In a model of portal hypertension we previously showed dynamic changes in the expression of MYPT1 isoforms in the portal vein and upstream mesenteric artery [4].
  • To optimise breast cancer screening protocols, risk (induction of fatal tumors) versus benefit (reduction in the number of fatal tumors) analyses are performed for a simulated stable Swedish female population, using the Model for evaluation of Breast cancer Screening (MBS) [5].

Psychiatry related information on PPP1R12A

  • The study was descriptive in design and used a semistructured interview format with four open-ended questions and a numerical self-assessment of dyspnea using the Modified 0-10 Borg Scale (MBS) [6].

High impact information on PPP1R12A

  • It is shown here that cGKIalpha is targeted to the smooth muscle cell contractile apparatus by a leucine zipper interaction with the myosin-binding subunit (MBS) of myosin phosphatase [7].
  • Uncoupling of the cGKIalpha-MBS interaction prevents cGMP-dependent dephosphorylation of myosin light chain, demonstrating that this interaction is essential to the regulation of vascular smooth muscle cell tone [7].
  • The guanosine triphosphate (GTP)-bound, active form of RhoA (GTP.RhoA) specifically interacted with the myosin-binding subunit (MBS) of myosin phosphatase, which regulates the extent of phosphorylation of MLC [8].
  • The crystal structure of the PP1 catalytic subunit in complex with the targeting subunit MYPT1 indicates that there is also scope for intimate phosphatase regulation by scaffold proteins [9].
  • We propose that CPI-17 binds at the PP1 active site where it is dephosphorylated, but association of MYPT1 with PP1C allosterically retards this hydrolysis, resulting in formation of a complex of MYPT1.PP1C.P-CPI-17, leading to an increase in smooth muscle contraction [10].

Chemical compound and disease context of PPP1R12A

  • The new automated Enzymun-Test anti-HBc Plus for the detection of antibodies to hepatitis B virus (HBV) core antigen (anti-HBc) after pretreatment with reducing agents dithiothreitol (25 degrees C; + DTT) or potassium bisulfite (37 degrees C; + MBS) was evaluated by testing 571 serum and plasma samples [11].

Biological context of PPP1R12A


Anatomical context of PPP1R12A


Associations of PPP1R12A with chemical compounds


Enzymatic interactions of PPP1R12A


Regulatory relationships of PPP1R12A


Other interactions of PPP1R12A


Analytical, diagnostic and therapeutic context of PPP1R12A


  1. Vascular dysfunction in human and rat cirrhosis: role of receptor-desensitizing and calcium-sensitizing proteins. Hennenberg, M., Trebicka, J., Biecker, E., Schepke, M., Sauerbruch, T., Heller, J. Hepatology (2007) [Pubmed]
  2. Sphingosine 1-phosphate causes airway hyper-reactivity by rho-mediated Myosin phosphatase inactivation. Kume, H., Takeda, N., Oguma, T., Ito, S., Kondo, M., Ito, Y., Shimokata, K. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  3. Ca2+-desensitizing hypoxic vasorelaxation: pivotal role for the myosin binding subunit of myosin phosphatase (MYPT1) in porcine coronary artery. Wardle, R.L., Gu, M., Ishida, Y., Paul, R.J. J. Physiol. (Lond.) (2006) [Pubmed]
  4. Myosin phosphatase isoform switching in vascular smooth muscle development. Payne, M.C., Zhang, H.Y., Prosdocimo, T., Joyce, K.M., Koga, Y., Ikebe, M., Fisher, S.A. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  5. Optimisation of mammographic breast cancer screening using a computer simulation model. Jansen, J.T., Zoetelief, J. European journal of radiology. (1997) [Pubmed]
  6. Acute dyspnea as perceived by patients with chronic obstructive pulmonary disease. Heinzer, M.M., Bish, C., Detwiler, R. Clinical nursing research. (2003) [Pubmed]
  7. Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase Ialpha. Surks, H.K., Mochizuki, N., Kasai, Y., Georgescu, S.P., Tang, K.M., Ito, M., Lincoln, T.M., Mendelsohn, M.E. Science (1999) [Pubmed]
  8. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, K., Iwamatsu, A., Kaibuchi, K. Science (1996) [Pubmed]
  9. Lining the pockets of kinases and phosphatases. Gold, M.G., Barford, D., Komander, D. Curr. Opin. Struct. Biol. (2006) [Pubmed]
  10. Phosphoprotein inhibitor CPI-17 specificity depends on allosteric regulation of protein phosphatase-1 by regulatory subunits. Eto, M., Kitazawa, T., Brautigan, D.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  11. Evaluation of the new automated enzymun-test anti-HBc plus for the detection of hepatitis B virus core antibody. Weber, B., Michl, U., Mühlbacher, A., Paggi, G., Bossi, V. Intervirology (1998) [Pubmed]
  12. Expression of RND proteins in human myometrium. Lartey, J., Gampel, A., Pawade, J., Mellor, H., Bernal, A.L. Biol. Reprod. (2006) [Pubmed]
  13. Integrin-linked kinase phosphorylates the myosin phosphatase target subunit at the inhibitory site in platelet cytoskeleton. Kiss, E., Murányi, A., Csortos, C., Gergely, P., Ito, M., Hartshorne, D.J., Erdodi, F. Biochem. J. (2002) [Pubmed]
  14. Myosin phosphatase targeting subunit 1 affects cell migration by regulating myosin phosphorylation and actin assembly. Xia, D., Stull, J.T., Kamm, K.E. Exp. Cell Res. (2005) [Pubmed]
  15. Localization of the gene coding for myosin phosphatase, target subunit 1 (MYPT1) to human chromosome 12q15-q21. Takahashi, N., Ito, M., Tanaka, J., Nakano, T., Kaibuchi, K., Odai, H., Takemura, K. Genomics (1997) [Pubmed]
  16. Inhibition of RhoA/Rho kinase pathway is involved in the beneficial effect of sildenafil on pulmonary hypertension. Guilluy, C., Sauzeau, V., Rolli-Derkinderen, M., Guérin, P., Sagan, C., Pacaud, P., Loirand, G. Br. J. Pharmacol. (2005) [Pubmed]
  17. Protein kinase C-catalyzed phosphorylation of an inhibitory phosphoprotein of myosin phosphatase is involved in human platelet secretion. Watanabe, Y., Ito, M., Kataoka, Y., Wada, H., Koyama, M., Feng, J., Shiku, H., Nishikawa, M. Blood (2001) [Pubmed]
  18. Agonist- and depolarization-induced signals for myosin light chain phosphorylation and force generation of cultured vascular smooth muscle cells. Woodsome, T.P., Polzin, A., Kitazawa, K., Eto, M., Kitazawa, T. J. Cell. Sci. (2006) [Pubmed]
  19. Ca2+-Independent, Inhibitory Effects of Cyclic Adenosine 5'-Monophosphate on Ca2+ Regulation of Phosphoinositide 3-Kinase C2{alpha}, Rho, and Myosin Phosphatase in Vascular Smooth Muscle. Azam, M.A., Yoshioka, K., Ohkura, S., Takuwa, N., Sugimoto, N., Sato, K., Takuwa, Y. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  20. Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase targeting subunit and inhibits myosin phosphatase activity. Murányi, A., Zhang, R., Liu, F., Hirano, K., Ito, M., Epstein, H.F., Hartshorne, D.J. FEBS Lett. (2001) [Pubmed]
  21. RhoA- and PKC-alpha-mediated phosphorylation of MYPT and its association with HSP27 in colonic smooth muscle cells. Patil, S.B., Bitar, K.N. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  22. Inhibition of RhoA-mediated SRF activation by p116Rip. Mulder, J., Ariaens, A., van Horck, F.P., Moolenaar, W.H. FEBS Lett. (2005) [Pubmed]
  23. Class II phosphoinositide 3-kinase alpha-isoform regulates Rho, myosin phosphatase and contraction in vascular smooth muscle. Wang, Y., Yoshioka, K., Azam, M.A., Takuwa, N., Sakurada, S., Kayaba, Y., Sugimoto, N., Inoki, I., Kimura, T., Kuwaki, T., Takuwa, Y. Biochem. J. (2006) [Pubmed]
  24. PDZ Domain-mediated interaction of interleukin-16 precursor proteins with myosin phosphatase targeting subunits. Bannert, N., Vollhardt, K., Asomuddinov, B., Haag, M., König, H., Norley, S., Kurth, R. J. Biol. Chem. (2003) [Pubmed]
  25. Molecular cloning and analysis of the 5'-flanking region of the human MYPT1 gene. Machida, H., Ito, M., Okamoto, R., Shiraki, K., Isaka, N., Hartshorne, D.J., Nakano, T. Biochim. Biophys. Acta (2001) [Pubmed]
  26. Gq/G13 signaling by ET-1 in smooth muscle: MYPT1 phosphorylation via ETA and CPI-17 dephosphorylation via ETB. Hersch, E., Huang, J., Grider, J.R., Murthy, K.S. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  27. Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. Wooldridge, A.A., MacDonald, J.A., Erdodi, F., Ma, C., Borman, M.A., Hartshorne, D.J., Haystead, T.A. J. Biol. Chem. (2004) [Pubmed]
  28. Spontaneously tonic smooth muscle has characteristically higher levels of RhoA/ROK compared with the phasic smooth muscle. Patel, C.A., Rattan, S. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  29. Okadaic acid induces phosphorylation and translocation of myosin phosphatase target subunit 1 influencing myosin phosphorylation, stress fiber assembly and cell migration in HepG2 cells. Lontay, B., Kiss, A., Gergely, P., Hartshorne, D.J., Erdodi, F. Cell. Signal. (2005) [Pubmed]
  30. Comparison of psychotropic drug intake in two populations in West Germany. Results from the Munich Blood Pressure Study 1980/81 and the Luebeck Blood Pressure Study 1984. Koenig, W., Rüther, E., Remmers, A., Keil, U. Pharmacopsychiatry (1987) [Pubmed]
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