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Gene Review

Npy4r  -  neuropeptide Y receptor Y4

Rattus norvegicus

Synonyms: NPY4-R, Neuropeptide Y receptor type 4, PP1, Pancreatic polypeptide receptor 1, Ppyr1
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Disease relevance of Ppyr1

  • PP1, an Src-family kinase inhibitor, reduced BBB permeability, brain edema, and mortality and decreased the phosphorylation of VEGF and MAPKs [1].
  • PP1 was also administered for 5 min before the sustained ischemia (late PP1 treatment) or after IPC (late PP1-PC treatment) [2].
  • We discuss the possibility that inhibition of PP1 and PP2A accounts for the extreme toxicity of microcystin-LR, and indicate its potential value in the detection and analysis of protein kinases and phosphatases [3].
  • Hypoxia decreased the activity of phosphatase-1 (PP-1) [4].
  • In a poorly differentiated hepatoma AH13, a line of rat ascites hepatoma, the mRNA level of PP1 alpha was 5.6 times higher than that of the control livers, whereas the mRNA lever of PP2C was almost the same as that of the control livers and the level of PP2A mRNA was distinctly lower than that of the control livers [5].

High impact information on Ppyr1

  • One form of LTD that has been observed in the hippocampus requires activation of postsynaptic NMDA (N-methyl-D-aspartate) receptors, a change in postsynaptic calcium concentration, and activation of postsynaptic serine/threonine protein phosphatase 1 (PP1) or 2A (PP2A) [6].
  • Stimulation that induced LTP triggered cAMP-dependent phosphorylation of endogenous inhibitor-1 and a decrease in PP1 activity [7].
  • One mechanism involves control of PP-1 catalytic activity by DARPP-32, a dopamine- and cAMP-regulated phosphoprotein highly enriched in neostriatum [8].
  • The results suggest that regulation of anchored PP-1 is important for AMPA-receptor-mediated synaptic transmission and plasticity [8].
  • In cultured neurons, synaptic activation of NMDA receptors increased the proportion of PP1 localized to synapses [9].

Chemical compound and disease context of Ppyr1

  • Tautomycin, a polyketide produced by the soil bacteria Streptomyces which inhibits serine/threonine phosphatases of the PP1/PP2A subgroup, was able to inhibit the endogenous phosphatase activity in a concentration-dependent form (Ki(app)=7.35 nM) [10].

Biological context of Ppyr1


Anatomical context of Ppyr1

  • D5 dopamine receptors enhance Zn2+-sensitive GABA(A) currents in striatal cholinergic interneurons through a PKA/PP1 cascade [15].
  • We investigated the role of postsynaptic protein phosphatase 1 (PP1) in regulating synaptic strength by loading CA1 pyramidal cells either with peptides that disrupt PP1 binding to synaptic targeting proteins or with active PP1 [9].
  • To investigate the function of Fyn activation on differentiation, we used Src family tyrosine kinase inhibitors, PP1 and PP2, in cultures of differentiating oligodendrocyte progenitors [16].
  • Protein phosphatase 1 (PP1) is greatly enriched in dendritic spines and has been implicated in both the regulation of ionic conductances and long-term synaptic plasticity [13].
  • In addition, the effect of cAMP on protein phosphatases 1 and 2A (PP1/2A) was determined in homogenates and plasma membranes obtained from CPT-cAMP-treated hepatocytes [17].

Associations of Ppyr1 with chemical compounds

  • In rat neostriatal neurons, D1 dopamine receptors regulate the activity of cyclic AMP-dependent protein kinase (PKA) and protein phosphatase 1 (PP1) [18].
  • Inhibition of protein phosphatase 1 (PP1) and/or protein phosphatase 2A (PP2A) by the specific inhibitor calyculin A occluded the PKA-mediated potentiation of striatal NMDA responses, suggesting that the PKA effect was mediated by inhibition of a protein phosphatase [19].
  • In contrast, M(2) mAChR internalization is not (or is only slightly) reduced by expression of these constructs or treatment with PP1 or genistein [20].
  • Okadaic acid and tautomycin, inhibitors of PP1/2A, inhibited cAMP-mediated increases in TC uptake and cytosolic [Ca2+], and only tautomycin inhibited basal TC uptake [21].
  • In this study, we examined the potential role of serine/threonine protein phosphatase-1 (PP-1) and PP-2A in the mechanism of Na+/K+-ATPase activation by insulin in the rat skeletal muscle cell line L6 [22].

Other interactions of Ppyr1


Analytical, diagnostic and therapeutic context of Ppyr1


  1. Signaling pathways for early brain injury after subarachnoid hemorrhage. Kusaka, G., Ishikawa, M., Nanda, A., Granger, D.N., Zhang, J.H. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
  2. Src tyrosine kinase is the trigger but not the mediator of ischemic preconditioning. Hattori, R., Otani, H., Uchiyama, T., Imamura, H., Cui, J., Maulik, N., Cordis, G.A., Zhu, L., Das, D.K. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  3. Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. MacKintosh, C., Beattie, K.A., Klumpp, S., Cohen, P., Codd, G.A. FEBS Lett. (1990) [Pubmed]
  4. Phosphorylation and hypoxia-induced heme oxygenase-1 gene expression in cardiomyocytes. Wu, G., Marín-García, J., Rogers, T.B., Lakatta, E.G., Long, X. J. Card. Fail. (2004) [Pubmed]
  5. mRNA levels of catalytic subunits of protein phosphatases 1, 2A, and 2C in hepatocarcinogenesis. Kitamura, K., Mizuno, Y., Hatayama, I., Sato, K., Tamura, S., Nagao, M., Tsuiki, S., Kikuchi, K. Jpn. J. Cancer Res. (1992) [Pubmed]
  6. Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression. Mulkey, R.M., Endo, S., Shenolikar, S., Malenka, R.C. Nature (1994) [Pubmed]
  7. Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP. Blitzer, R.D., Connor, J.H., Brown, G.P., Wong, T., Shenolikar, S., Iyengar, R., Landau, E.M. Science (1998) [Pubmed]
  8. Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP-32 and spinophilin. Yan, Z., Hsieh-Wilson, L., Feng, J., Tomizawa, K., Allen, P.B., Fienberg, A.A., Nairn, A.C., Greengard, P. Nat. Neurosci. (1999) [Pubmed]
  9. Regulation of synaptic strength by protein phosphatase 1. Morishita, W., Connor, J.H., Xia, H., Quinlan, E.M., Shenolikar, S., Malenka, R.C. Neuron (2001) [Pubmed]
  10. Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor. Piwien-Pilipuk, G., Galigniana, M.D. Mol. Cell. Endocrinol. (1998) [Pubmed]
  11. Ultrarapid caspase-3 dependent apoptosis induction by serine/threonine phosphatase inhibitors. Fladmark, K.E., Brustugun, O.T., Hovland, R., Boe, R., Gjertsen, B.T., Zhivotovsky, B., Døskeland, S.O. Cell Death Differ. (1999) [Pubmed]
  12. Roles of protein kinase C, Ca2+, Pyk2, and c-Src in agonist activation of rat lacrimal gland p42/p44 MAPK. Hodges, R.R., Rios, J.D., Vrouvlianis, J., Ota, I., Zoukhri, D., Dartt, D.A. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  13. Spinophilin, a novel protein phosphatase 1 binding protein localized to dendritic spines. Allen, P.B., Ouimet, C.C., Greengard, P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  14. The alpha and gamma 1 isoforms of protein phosphatase 1 are highly and specifically concentrated in dendritic spines. Ouimet, C.C., da Cruz e Silva, E.F., Greengard, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  15. D5 dopamine receptors enhance Zn2+-sensitive GABA(A) currents in striatal cholinergic interneurons through a PKA/PP1 cascade. Yan, Z., Surmeier, D.J. Neuron (1997) [Pubmed]
  16. Morphological differentiation of oligodendrocytes requires activation of Fyn tyrosine kinase. Osterhout, D.J., Wolven, A., Wolf, R.M., Resh, M.D., Chao, M.V. J. Cell Biol. (1999) [Pubmed]
  17. Sodium taurocholate cotransporting polypeptide is a serine, threonine phosphoprotein and is dephosphorylated by cyclic adenosine monophosphate. Mukhopadhyay, S., Ananthanarayanan, M., Stieger, B., Meier, P.J., Suchy, F.J., Anwer, M.S. Hepatology (1998) [Pubmed]
  18. Modulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons. Surmeier, D.J., Bargas, J., Hemmings, H.C., Nairn, A.C., Greengard, P. Neuron (1995) [Pubmed]
  19. The phosphoprotein DARPP-32 mediates cAMP-dependent potentiation of striatal N-methyl-D-aspartate responses. Blank, T., Nijholt, I., Teichert, U., Kügler, H., Behrsing, H., Fienberg, A., Greengard, P., Spiess, J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  20. Essential role of dynamin in internalization of M2 muscarinic acetylcholine and angiotensin AT1A receptors. Werbonat, Y., Kleutges, N., Jakobs, K.H., van Koppen, C.J. J. Biol. Chem. (2000) [Pubmed]
  21. Role of protein phosphatases in cyclic AMP-mediated stimulation of hepatic Na+/taurocholate cotransport. Mukhopadhyay, S., Webster, C.R., Anwer, M.S. J. Biol. Chem. (1998) [Pubmed]
  22. Role of serine/threonine protein phosphatases in insulin regulation of Na+/K+-ATPase activity in cultured rat skeletal muscle cells. Ragolia, L., Cherpalis, B., Srinivasan, M., Begum, N. J. Biol. Chem. (1997) [Pubmed]
  23. Neuropeptide Y and pancreatic polypeptide reduce calcium currents in acutely dissociated neurons from adult rat superior cervical ganglia. Foucart, S., Bleakman, D., Bindokas, V.P., Miller, R.J. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  24. Differential expression of protein phosphatase 1 isoforms in mammalian brain. da Cruz e Silva, E.F., Fox, C.A., Ouimet, C.C., Gustafson, E., Watson, S.J., Greengard, P. J. Neurosci. (1995) [Pubmed]
  25. Inhibition of myogenesis by depletion of the glycogen-associated regulatory subunit of protein phosphatase-1 in rat skeletal muscle cells. Ragolia, L., Zuo, Q., Begum, N. J. Biol. Chem. (2000) [Pubmed]
  26. Regulation of protein phosphatase 1 and 2A activities by insulin during myogenesis in rat skeletal muscle cells in culture. Srinivasan, M., Begum, N. J. Biol. Chem. (1994) [Pubmed]
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