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Gene Review

Inpp5d  -  inositol polyphosphate-5-phosphatase D

Mus musculus

Synonyms: 7a33, AI323613, Inositol polyphosphate-5-phosphatase of 145 kDa, Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1, SH2 domain-containing inositol 5'-phosphatase 1, ...
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Disease relevance of Inpp5d

  • Indeed Lyn-deficient mice are hyper-responsive to myeloid growth factors and develop a myeloproliferative disorder that predisposes the mice to macrophage tumours, with loss of negative regulation through SHP-1 and SHIP-1 thought to be the major contributing factor to this phenotype [1].
  • Accordingly, SHIP1-null mice showed defects in arterial thrombus formation in response to a localized laser-induced injury [2].

High impact information on Inpp5d


Biological context of Inpp5d


Anatomical context of Inpp5d


Associations of Inpp5d with chemical compounds

  • When coaggregated with ITAM-bearing receptors, FcgammaRIIB become tyrosyl-phosphorylated and recruit the Src homology 2 (SH2) domain-containing inositol 5'-phosphatases SHIP1 and SHIP2, which mediate inhibition [14].
  • We show here that a second tyrosine-containing motif in the intracytoplasmic domain of FcgammaRIIB is required for SHIP1/2 to be coprecipitated with the receptor [14].
  • Our studies on murine SHIP1 knockout platelets have defined a major role for this enzyme in regulating integrin alpha(IIb)beta(3)-dependent phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) accumulation, necessary for a cytosolic calcium response and platelet spreading [15].
  • Differences in signaling pathways and expression level of the phosphoinositide phosphatase SHIP1 between two oncogenic mutants of the receptor tyrosine kinase KIT [16].
  • Utilizing a glutathione S-transferase fusion protein, we found that SHIP-1 bound to Lyn via the SHIP-1 Src homology 2 domain [17].
  • Imaging reactive oxygen intermediate activities in phagosomes revealed decreased early NADPH oxidase activity in SHIP-1-deficient macrophages [18].
  • Overall, activation of G protein-coupled receptors that raise cyclic AMP cause SHIP1 to be phosphorylated and stimulate its inositol phosphatase activity [19].

Physical interactions of Inpp5d


Regulatory relationships of Inpp5d


Other interactions of Inpp5d


Analytical, diagnostic and therapeutic context of Inpp5d


  1. The duplicitous nature of the Lyn tyrosine kinase in growth factor signaling. Hibbs, M.L., Harder, K.W. Growth Factors (2006) [Pubmed]
  2. Deficiency of Src homology 2 domain-containing inositol 5-phosphatase 1 affects platelet responses and thrombus growth. Séverin, S., Gratacap, M.P., Lenain, N., Alvarez, L., Hollande, E., Penninger, J.M., Gachet, C., Plantavid, M., Payrastre, B. J. Clin. Invest. (2007) [Pubmed]
  3. A dual role for Src homology 2 domain-containing inositol-5-phosphatase (SHIP) in immunity: aberrant development and enhanced function of b lymphocytes in ship -/- mice. Helgason, C.D., Kalberer, C.P., Damen, J.E., Chappel, S.M., Pineault, N., Krystal, G., Humphries, R.K. J. Exp. Med. (2000) [Pubmed]
  4. The inositol polyphosphate 5-phosphatase ship is a crucial negative regulator of B cell antigen receptor signaling. Liu, Q., Oliveira-Dos-Santos, A.J., Mariathasan, S., Bouchard, D., Jones, J., Sarao, R., Kozieradzki, I., Ohashi, P.S., Penninger, J.M., Dumont, D.J. J. Exp. Med. (1998) [Pubmed]
  5. Redirection of B cell responsiveness by transforming growth factor beta receptor. Roes, J., Choi, B.K., Cazac, B.B. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. The inositol phosphatase SHIP-2 down-regulates FcgammaR-mediated phagocytosis in murine macrophages independently of SHIP-1. Ai, J., Maturu, A., Johnson, W., Wang, Y., Marsh, C.B., Tridandapani, S. Blood (2006) [Pubmed]
  7. Embryonic and hematopoietic stem cells express a novel SH2-containing inositol 5'-phosphatase isoform that partners with the Grb2 adapter protein. Tu, Z., Ninos, J.M., Ma, Z., Wang, J.W., Lemos, M.P., Desponts, C., Ghansah, T., Howson, J.M., Kerr, W.G. Blood (2001) [Pubmed]
  8. IL-6 blocks a discrete early step in lymphopoiesis. Maeda, K., Baba, Y., Nagai, Y., Miyazaki, K., Malykhin, A., Nakamura, K., Kincade, P.W., Sakaguchi, N., Coggeshall, K.M. Blood (2005) [Pubmed]
  9. Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1. Harder, K.W., Quilici, C., Naik, E., Inglese, M., Kountouri, N., Turner, A., Zlatic, K., Tarlinton, D.M., Hibbs, M.L. Blood (2004) [Pubmed]
  10. Src homology 2 domain-containing inositol 5-phosphatase 1 mediates cell cycle arrest by FcgammaRIIB. Malbec, O., Schmitt, C., Bruhns, P., Krystal, G., Fridman, W.H., Daëron, M. J. Biol. Chem. (2001) [Pubmed]
  11. Src homology 2 domain-containing inositol-5-phosphatase 1 (SHIP1) negatively regulates TLR4-mediated LPS response primarily through a phosphatase activity- and PI-3K-independent mechanism. An, H., Xu, H., Zhang, M., Zhou, J., Feng, T., Qian, C., Qi, R., Cao, X. Blood (2005) [Pubmed]
  12. Distribution of the src-homology-2-domain-containing inositol 5-phosphatase SHIP-2 in both non-haemopoietic and haemopoietic cells and possible involvement of SHIP-2 in negative signalling of B-cells. Muraille, E., Pesesse, X., Kuntz, C., Erneux, C. Biochem. J. (1999) [Pubmed]
  13. Src homology 2-containing inositol 5'-phosphatase 1 negatively regulates IFN-gamma production by natural killer cells stimulated with antibody-coated tumor cells and interleukin-12. Parihar, R., Trotta, R., Roda, J.M., Ferketich, A.K., Tridandapani, S., Caligiuri, M.A., Carson, W.E. Cancer Res. (2005) [Pubmed]
  14. Two distinct tyrosine-based motifs enable the inhibitory receptor FcgammaRIIB to cooperatively recruit the inositol phosphatases SHIP1/2 and the adapters Grb2/Grap. Isnardi, I., Lesourne, R., Bruhns, P., Fridman, W.H., Cambier, J.C., Daëron, M. J. Biol. Chem. (2004) [Pubmed]
  15. SHIP1 and Lyn Kinase Negatively Regulate Integrin alpha IIb beta 3 signaling in platelets. Maxwell, M.J., Yuan, Y., Anderson, K.E., Hibbs, M.L., Salem, H.H., Jackson, S.P. J. Biol. Chem. (2004) [Pubmed]
  16. Differences in signaling pathways and expression level of the phosphoinositide phosphatase SHIP1 between two oncogenic mutants of the receptor tyrosine kinase KIT. Vanderwinden, J.M., Wang, D., Paternotte, N., Mignon, S., Isozaki, K., Erneux, C. Cell. Signal. (2006) [Pubmed]
  17. The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity. Baran, C.P., Tridandapani, S., Helgason, C.D., Humphries, R.K., Krystal, G., Marsh, C.B. J. Biol. Chem. (2003) [Pubmed]
  18. SHIP-1 increases early oxidative burst and regulates phagosome maturation in macrophages. Kamen, L.A., Levinsohn, J., Cadwallader, A., Tridandapani, S., Swanson, J.A. J. Immunol. (2008) [Pubmed]
  19. Regulation of the Src homology 2 domain-containing inositol 5'-phosphatase (SHIP1) by the cyclic AMP-dependent protein kinase. Zhang, J., Walk, S.F., Ravichandran, K.S., Garrison, J.C. J. Biol. Chem. (2009) [Pubmed]
  20. Dynamic interactions of Fc gamma receptor IIB with filamin-bound SHIP1 amplify filamentous actin-dependent negative regulation of Fc epsilon receptor I signaling. Lesourne, R., Fridman, W.H., Daëron, M. J. Immunol. (2005) [Pubmed]
  21. The role of SHIP1 in macrophage programming and activation. Rauh, M.J., Sly, L.M., Kalesnikoff, J., Hughes, M.R., Cao, L.P., Lam, V., Krystal, G. Biochem. Soc. Trans. (2004) [Pubmed]
  22. TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways. Ho, J.M., Nguyen, M.H., Dierov, J.K., Badger, K.M., Beattie, B.K., Tartaro, P., Haq, R., Zanke, B.W., Carroll, M.P., Barber, D.L. Blood (2002) [Pubmed]
  23. IVIg-mediated amelioration of murine ITP via FcgammaRIIB is independent of SHIP1, SHP-1, and Btk activity. Crow, A.R., Song, S., Freedman, J., Helgason, C.D., Humphries, R.K., Siminovitch, K.A., Lazarus, A.H. Blood (2003) [Pubmed]
  24. The FcepsilonRIbeta immunoreceptor tyrosine-based activation motif exerts inhibitory control on MAPK and IkappaB kinase phosphorylation and mast cell cytokine production. Furumoto, Y., Nunomura, S., Terada, T., Rivera, J., Ra, C. J. Biol. Chem. (2004) [Pubmed]
  25. An incident of elevated levels of unsaturated free fatty acids in mussels from Nova Scotia and their toxic effect in mice after intraperitoneal injection. Lawrence, J.F., Chadha, R.K., Ratnayake, W.M., Truelove, J.F. Nat. Toxins (1994) [Pubmed]
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