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Gene Review

Phospho1  -  phosphatase, orphan 1

Mus musculus

Synonyms: D11Moh36, Phosphoethanolamine/phosphocholine phosphatase, Phospo1
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Disease relevance of Phospho1


Psychiatry related information on Phospho1

  • Interestingly, the number of cells immunostaining for phospho-CREB (on Ser(133)) in the medial preoptic area of the hypothalamus, a key region for the expression of maternal behavior, increased nearly three-fold in wild-type mice following exposure to pups but not to novel objects [6].

High impact information on Phospho1

  • Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy [7].
  • Ligands with similar K(D)s induce similar amounts of total phospho-zeta but distinct patterns of zeta phosphorylation [8].
  • Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization [9].
  • Both the dephospho form (which blocks binding of GRIP/ABP and PICK1) and the phospho form (which selectively blocks PICK1) attenuated LTD induction by glutamate/depolarization pairing, as did antibodies directed against the PDZ domain of PICK1 [10].
  • A phospho-switch controls the dynamic association of synapsins with synaptic vesicles [11].

Chemical compound and disease context of Phospho1

  • Culturing embryonic cortical neurons and differentiated SH-SY-5Y human neuroblastoma cells in folate-free medium induced neurodegenerative changes characteristic of those observed in AD, including increased cytosolic calcium, reactive oxygen species (ROS), phospho-tau and apoptosis [12].
  • Ethanol (1.5-3.5 g/kg body weight) was administered intraperitoneally to mice and the phosphorylation of MAP (mitogen-activated protein) kinase in the cerebral cortex was determined using phospho-specific MAP kinase antibodies [13].
  • RESULTS: Young adult mice were injected in the thymus with lentiviral vectors expressing eGFP or the hemaglutinin of the Influenza virus under the control of the ubiquitous phospho glycerate kinase promoter [14].
  • The initial detection of caspase-3 cleavage occurring in G(2)-M arrest was independent of a change in phospho-cdc2 (Tyr(15)) protein; consequently, sulforaphane treatment combined with UCN-01 had no significant impact on cellular toxicity [15].

Biological context of Phospho1

  • Deregulated Myc expression induces DNA damage in primary transgenic keratinocytes and the formation of gammaH2AX and phospho-SMC1 foci in transgenic tissue [16].
  • Disruption of B-raf significantly reduced the levels of phospho-ERK1/2 and, surprisingly, induced an approximately 1.5-fold increase in cell migration [17].
  • Using serum-stimulated mouse alveolar type II epithelial cells as a model for cell cycle reentry, we show that the duration of phospho-ERK1/2 in the nucleus determines cell fate in response to crocidolite asbestos [18].
  • Higher levels of asbestos (1.0 to 5.0 microg/cm2) prolonged the localization of phospho-ERK1/2 in the nucleus in the presence of high serum, impeded S-phase entry, and induced apoptosis in a dose-dependent manner [18].
  • MBsep exists as a phospho-protein when expressed in Sf9 cells and the immunoprecipitated mBsep complex is a substrate for the catalytic subunit of PKC [19].

Anatomical context of Phospho1

  • In resting T cell clones, presentation with APL/live APC stimulated a unique pattern of TCR phospho-zeta species and a subsequent lack of association with zap70 [7].
  • We have used phospho-specific antibodies to re-examine the multisite phosphorylation of c-Jun in murine RAW macrophages and embryonic fibroblasts [20].
  • Singly S-acylated LCK mutants, which were expressed in part at the plasma membrane, efficiently reconstituted the induced association of phospho-zeta with ZAP-70 and intracellular Ca2+ fluxes triggered by the TCR [21].
  • Immunostaining demonstrated that, like Rp1, phospho-JNKs and phospho-MAP2 are present in outer segments of photoreceptors [22].
  • A phospho-mimicking mutant, WASp-Y291E, exhibited an enhanced ability to stimulate actin polymerization in a cell-free system and when microinjected into primary macrophages induced extensive filopodium formation with greater efficiency than wild-type WASp or a Y291F mutant [23].

Associations of Phospho1 with chemical compounds


Physical interactions of Phospho1

  • We proposed that the SH2 domain of SHIP competes with Grb2 in binding to phospho-Shc, resulting in a block in Ras signaling [29].

Regulatory relationships of Phospho1

  • RSK-1 phosphorylation was also rhythmically regulated within a subset of phospho-ERK-expressing cells [30].
  • In addition, we identify a multifunctional protein named B23 that strongly cross-reacts with a phospho-MEK antibody in mitotic cells [31].

Other interactions of Phospho1

  • The increased phospho-Stat3 levels correlated with increased Shp-2Delta46-110 ES cell secondary EB formation and survival [32].
  • By using wild-type and mutated forms of merlin and phospho-directed antibodies, we show that phosphorylation of merlin at serine 518 leads to dramatic protein relocalization [33].
  • Other blots showed the specific appearance of the phosphorylated EGFR and of phospho-ERK-1/2 in response to EGF [34].
  • The rescued palatal fusion in Tgf-beta3-/-/K14-Smad2 mice, however, never proceeded to the junction of primary and secondary palates and the most posterior border of the soft palate, despite phospho-SMAD2 expression in these regions at the same level as in the middle portion of the secondary palate [35].
  • Interestingly, the levels of anti-apoptotic phospho-Bad (Ser155 and Ser112) had a biphasic increase after B[a]P or CPP treatment [36].

Analytical, diagnostic and therapeutic context of Phospho1


  1. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. Novoa, I., Zeng, H., Harding, H.P., Ron, D. J. Cell Biol. (2001) [Pubmed]
  2. The S100A7-c-Jun activation domain binding protein 1 pathway enhances prosurvival pathways in breast cancer. Emberley, E.D., Niu, Y., Curtis, L., Troup, S., Mandal, S.K., Myers, J.N., Gibson, S.B., Murphy, L.C., Watson, P.H. Cancer Res. (2005) [Pubmed]
  3. Caveolin-3 knock-out mice develop a progressive cardiomyopathy and show hyperactivation of the p42/44 MAPK cascade. Woodman, S.E., Park, D.S., Cohen, A.W., Cheung, M.W., Chandra, M., Shirani, J., Tang, B., Jelicks, L.A., Kitsis, R.N., Christ, G.J., Factor, S.M., Tanowitz, H.B., Lisanti, M.P. J. Biol. Chem. (2002) [Pubmed]
  4. Microglia recognize double-stranded RNA via TLR3. Town, T., Jeng, D., Alexopoulou, L., Tan, J., Flavell, R.A. J. Immunol. (2006) [Pubmed]
  5. Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition. Dudkin, L., Dilling, M.B., Cheshire, P.J., Harwood, F.C., Hollingshead, M., Arbuck, S.G., Travis, R., Sausville, E.A., Houghton, P.J. Clin. Cancer Res. (2001) [Pubmed]
  6. Cyclic AMP response element-binding protein is required for normal maternal nurturing behavior. Jin, S.H., Blendy, J.A., Thomas, S.A. Neuroscience (2005) [Pubmed]
  7. Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy. Sloan-Lancaster, J., Shaw, A.S., Rothbard, J.B., Allen, P.M. Cell (1994) [Pubmed]
  8. High- and low-potency ligands with similar affinities for the TCR: the importance of kinetics in TCR signaling. Kersh, G.J., Kersh, E.N., Fremont, D.H., Allen, P.M. Immunity (1998) [Pubmed]
  9. Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. del Pozo, M.A., Balasubramanian, N., Alderson, N.B., Kiosses, W.B., Grande-García, A., Anderson, R.G., Schwartz, M.A. Nat. Cell Biol. (2005) [Pubmed]
  10. Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Xia, J., Chung, H.J., Wihler, C., Huganir, R.L., Linden, D.J. Neuron (2000) [Pubmed]
  11. A phospho-switch controls the dynamic association of synapsins with synaptic vesicles. Hosaka, M., Hammer, R.E., Südhof, T.C. Neuron (1999) [Pubmed]
  12. Folate deprivation induces neurodegeneration: roles of oxidative stress and increased homocysteine. Ho, P.I., Ashline, D., Dhitavat, S., Ortiz, D., Collins, S.C., Shea, T.B., Rogers, E. Neurobiol. Dis. (2003) [Pubmed]
  13. Ethanol-mediated inhibition of mitogen-activated protein kinase phosphorylation in mouse brain. Kalluri, H.S., Ticku, M.K. Eur. J. Pharmacol. (2002) [Pubmed]
  14. In situ transduction of stromal cells and thymocytes upon intrathymic injection of lentiviral vectors. Marodon, G., Klatzmann, D. BMC Immunol. (2004) [Pubmed]
  15. The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice. Pham, N.A., Jacobberger, J.W., Schimmer, A.D., Cao, P., Gronda, M., Hedley, D.W. Mol. Cancer Ther. (2004) [Pubmed]
  16. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc. Pusapati, R.V., Rounbehler, R.J., Hong, S., Powers, J.T., Yan, M., Kiguchi, K., McArthur, M.J., Wong, P.K., Johnson, D.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  17. B-Raf acts via the ROCKII/LIMK/cofilin pathway to maintain actin stress fibers in fibroblasts. Pritchard, C.A., Hayes, L., Wojnowski, L., Zimmer, A., Marais, R.M., Norman, J.C. Mol. Cell. Biol. (2004) [Pubmed]
  18. The duration of nuclear extracellular signal-regulated kinase 1 and 2 signaling during cell cycle reentry distinguishes proliferation from apoptosis in response to asbestos. Yuan, Z., Taatjes, D.J., Mossman, B.T., Heintz, N.H. Cancer Res. (2004) [Pubmed]
  19. Characterization of the mouse bile salt export pump overexpressed in the baculovirus system. Noe, J., Hagenbuch, B., Meier, P.J., St-Pierre, M.V. Hepatology (2001) [Pubmed]
  20. A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun. Morton, S., Davis, R.J., McLaren, A., Cohen, P. EMBO J. (2003) [Pubmed]
  21. S-acylation of LCK protein tyrosine kinase is essential for its signalling function in T lymphocytes. Kabouridis, P.S., Magee, A.I., Ley, S.C. EMBO J. (1997) [Pubmed]
  22. Distinct gene expression profiles and reduced JNK signaling in retinitis pigmentosa caused by RP1 mutations. Liu, J., Huang, Q., Higdon, J., Liu, W., Xie, T., Yamashita, T., Cheon, K., Cheng, C., Zuo, J. Hum. Mol. Genet. (2005) [Pubmed]
  23. Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein. Cory, G.O., Garg, R., Cramer, R., Ridley, A.J. J. Biol. Chem. (2002) [Pubmed]
  24. RhoE function is regulated by ROCK I-mediated phosphorylation. Riento, K., Totty, N., Villalonga, P., Garg, R., Guasch, R., Ridley, A.J. EMBO J. (2005) [Pubmed]
  25. ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation. Gille, H., Kortenjann, M., Thomae, O., Moomaw, C., Slaughter, C., Cobb, M.H., Shaw, P.E. EMBO J. (1995) [Pubmed]
  26. Insulin-stimulated microtubule-associated protein kinase is phosphorylated on tyrosine and threonine in vivo. Ray, L.B., Sturgill, T.W. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  27. S6 kinase in quiescent Swiss mouse 3T3 cells is activated by phosphorylation in response to serum treatment. Ballou, L.M., Siegmann, M., Thomas, G. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  28. Membranes from T and B lymphocytes have different patterns of tyrosine phosphorylation. Earp, H.S., Austin, K.S., Buessow, S.C., Dy, R., Gillespie, G.Y. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  29. Activation-induced bi-dentate interaction of SHIP and Shc in B lymphocytes. Pradhan, M., Coggeshall, K.M. J. Cell. Biochem. (1997) [Pubmed]
  30. Light- and clock-dependent regulation of ribosomal S6 kinase activity in the suprachiasmatic nucleus. Butcher, G.Q., Lee, B., Hsieh, F., Obrietan, K. Eur. J. Neurosci. (2004) [Pubmed]
  31. MEK inhibition and phosphorylation of serine 4 on B23 are two coincident events in mitosis. Hayne, C., Xiang, X., Luo, Z. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  32. A definitive role of Shp-2 tyrosine phosphatase in mediating embryonic stem cell differentiation and hematopoiesis. Chan, R.J., Johnson, S.A., Li, Y., Yoder, M.C., Feng, G.S. Blood (2003) [Pubmed]
  33. Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. Kissil, J.L., Johnson, K.C., Eckman, M.S., Jacks, T. J. Biol. Chem. (2002) [Pubmed]
  34. The ERK-1/2 signaling pathway is involved in the stimulation of branching morphogenesis of fetal mouse submandibular glands by EGF. Kashimata, M., Sayeed, S., Ka, A., Onetti-Muda, A., Sakagami, H., Faraggiana, T., Gresik, E.W. Dev. Biol. (2000) [Pubmed]
  35. Overexpression of Smad2 in Tgf-beta3-null mutant mice rescues cleft palate. Cui, X.M., Shiomi, N., Chen, J., Saito, T., Yamamoto, T., Ito, Y., Bringas, P., Chai, Y., Shuler, C.F. Dev. Biol. (2005) [Pubmed]
  36. Polycyclic aromatic hydrocarbons induce both apoptotic and anti-apoptotic signals in Hepa1c1c7 cells. Solhaug, A., Refsnes, M., Låg, M., Schwarze, P.E., Husøy, T., Holme, J.A. Carcinogenesis (2004) [Pubmed]
  37. Activation of B-Raf kinase requires phosphorylation of the conserved residues Thr598 and Ser601. Zhang, B.H., Guan, K.L. EMBO J. (2000) [Pubmed]
  38. Bombesin, vasopressin, and endothelin rapidly stimulate tyrosine phosphorylation in intact Swiss 3T3 cells. Zachary, I., Gil, J., Lehmann, W., Sinnett-Smith, J., Rozengurt, E. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  39. Cell cycle-dependent phosphorylation of mammalian protein phosphatase 1 by cdc2 kinase. Kwon, Y.G., Lee, S.Y., Choi, Y., Greengard, P., Nairn, A.C. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  40. DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein: regional, tissue, and phylogenetic distribution. Hemmings, H.C., Greengard, P. J. Neurosci. (1986) [Pubmed]
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