Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

SHIP

  • Matthew D. Blunt
  • Stephen G. Ward
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_271

Synonyms

Historical Background

SH2 domain-containing inositol phosphatase-1 (SHIP) was initially identified in 1994 as a tyrosine-phosphorylated protein after stimulation of blood cells by a broad number of cytokines and growth factors (Lioubin et al. 1994; Liu et al. 1994). It translocates to the plasma membrane after extracellular stimulation and hydrolyses the  phosphoinositide 3-kinase (PI3K)-generated second messenger PI(3,4, 5)P3, to PI(3,4)P2. As a result, SHIP is able to modulate PI(3,4,5)P3-mediated signaling and hence the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. The creation of germ-line SHIP–/– knockout mice in 1998 was instrumental in determining the role SHIP plays in the immune system (Helgason et al. 1998). Subsequent cell-restricted deletion in lymphoid and myeloid compartments some 10 years later, further...

This is a preview of subscription content, log in to check access.

References

  1. Avota E, Harms H, Schneider-Schaulies S. Measles virus induces expression of SIP110, a constitutively membrane clustered lipid phosphatase, which inhibits T cell proliferation. Cell Microbiol. 2006;8:1826–39.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Brooks R, Fuhler GM, Iyer S, Smith MJ, Park MY, Paraiso KH, Engelman RW, Kerr WG. SHIP1 inhibition increases immunoregulatory capacity and triggers apoptosis of hematopoietic cancer cells. J Immunol. 2010;184:3582–9.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Charlier E, Conde C, Zhang J, Deneubourg L, Di Valentin E, Rahmouni S, Chariot A, Agostinis P, Pang PC, Haslam SM, Dell A, Penninger J, Erneux C, Piette J, Gloire G. SHIP-1 inhibits CD95/APO-1/Fas-induced apoptosis in primary T lymphocytes and T leukemic cells by promoting CD95 glycosylation independently of its phosphatase activity. Leukemia. 2010;24:821–32.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Costinean S, Sandhu SK, Pedersen IM, Tili E, Trotta R, Perrotti D, Ciarlariello D, Neviani P, Harb J, Kauffman LR, Shidham A, Croce CM. Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein-beta are targeted by miR-155 in B cells of E{micro}-MiR-155 transgenic mice. Blood. 2009;114:1374–82.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ghansah T, Paraiso KHT, Highfill S, Desponts C, May S, McIntosh JK, Wang J-W, Ninos J, Brayer J, Cheng F, Sotomayor E, Kerr WG. Expansion of myeloid suppressor cells in SHIP-deficient mice represses allogeneic T cell responses. J Immunol. 2004;173:7324–30.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Hamilton MJ, Ho VW, Kuroda E, Ruschmann J, Antignano F, Lam V, Krystal G. Role of SHIP in cancer. Exp Hematol. 2011;39:2–13.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Harris SJ, Parry RV, Westwick J, Ward SG. Phosphoinositide lipid phosphatases: natural regulators of phosphoinositide 3-kinase signaling in T lymphocytes. J Biol Chem. 2008;283:2465–9.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Helgason CD, Damen JE, Rosten P, Grewal R, Sorensen P, Chappel SM, Borowski A, Jirik F, Krystal G, Humphries RK. Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span. Genes Dev. 1998;12:1610–20.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Hollander MC, Blumenthal GM, Dennis PA. PTEN loss in the continuum of common cancers, rare syndromes and mouse models. Nat Rev Cancer. 2011;11:289–301.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Kerr WGA. Role for SHIP in stem cell biology and transplantation. Curr Stem Cell Res Ther. 2008;3:99–106.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Kerr WG. Inhibitor and activator: dual functions for SHIP in immunity and cancer. Ann N Y Acad Sci. 2011;1217:1–17.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Lemmon MA, Ferguson KM. Signal-dependent membrane targeting by pleckstrin homology (PH) domains. Biochem J. 2000;350:1–18.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Leung WH, Tarasenko T, Bolland S. Differential roles for the inositol phosphatase SHIP in the regulation of macrophages and lymphocytes. Immunol Res. 2009;43:243–51.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Lioubin MN, Myles GM, Carlberg K, Bowtell D, Rohrschneider LR. Shc, Grb2, Sos1, and a 150-kilodalton tyrosine-phosphorylated protein form complexes with Fms in hematopoietic cells. Mol Cell Biol. 1994;14:5682–91.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Liu L, Damen JE, Cutler RL, Krystal G. Multiple cytokines stimulate the binding of a common 145-kilodalton protein to Shc at the Grb2 recognition site of Shc. Mol Cell Biol. 1994;14:6926–35.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007;129:1261–74.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Ono M, Bolland S, Tempst P, Ravetch JV. Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc?RIIB. Nature. 1996;383:263–6.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Ooms LM, Horan KA, Rahman P, Seaton G, Gurung R, Kethesparan DS, Mitchell CA. The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease. Biochem J. 2009;419:29–49.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Peng Q, Malhotra S, Torchia JA, Kerr WG, Coggeshall KM, Humphrey MB. TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. Sci Signal. 2010;3:ra38.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Shenker BJ, Dlakic M, Walker LP, Besack D, Jaffe E, LaBelle E, Boesze-Battaglia K. A novel mode of action for a microbial-derived immunotoxin: the cytolethal distending toxin subunit B exhibits phosphatidylinositol 3,4,5-triphosphate phosphatase activity. J Immunol. 2007;178:5099–108.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Matthew D. Blunt
    • 1
  • Stephen G. Ward
    • 2
  1. 1.Department of Pharmacy and PharmacologyUniversity of BathBathUK
  2. 2.Department of Pharmacy and PharmacologyUniversity of Bath, Claverton DownBathUK