INPP5D
Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1 (SHIP1) is an
endothelial cells.[10] This phosphatase is important for the regulation of cellular activation. Not only catalytic but also adaptor activities of this protein are involved in this process. Its movement from the cytosol to the cytoplasmic membrane, where predominantly performs its function, is mediated by tyrosine phosphorylation of the intracellular chains of cell surface receptors that SHIP1 binds. Insufficient regulation of SHIP1 leads to different pathologies.[11]
Structure and regulation of activity
SHIP1 is a 145 kDa large protein and member of the
isoforms, have been characterized.[7]
At the N-terminus of the protein, SH2 domain is formed. This domain is important for the interaction of SHIP1 with the phosphorylated protein chains that SHIP1 binds. Highly conserved phosphatase domain is in central part of the protein. This catalytic domain is flanked on the N-terminal side by the PH-like domain that binds phosphatidylinositol-3,4,5-triphosphate (PI(3,4,5)P3) and is overlapped on C-terminus with the C2 domain that binds phosphatidylinositol-3,4-bisphosphate (PI(4, 5)P2). The C-tail is not structured, but contains a proline-rich region that forms the motif for binding SH3 domain and also contains sequence containing tyrosine 915 (Y915) and tyrosine 1022 (Y1022) (in human cell) that is typical for interaction with the phosphotyrosine binding domain (PTB domain).
Phosphatase activity of SHIP1 can be allosteric regulated by phosphorylation of the catalytic domain on serine 440 (Ser440), this phosphorylation is mediated by cAMP-dependent protein kinase A (PKA).[12] Second allosteric regulation is mediated by binding PI(3,4)P2 to the C2 domain.[13] Furthermore, binding PDB domain to C-terminus of SHIP1 is regulated by Y915 and Y1022 phosphorylation.[14]
Function
At the plasma membrane, the protein
FcγRIIB inhibits the activation of B cells including Ca2+ influx.[15] SHIP1 can also interact with other inhibitory receptors and contribute to negative signaling.[16][17] Overall, the protein functions as a negative regulator of cell proliferation and survival. Nevertheless, SHIP1 may also bind to partially phosphorylated immunoreceptor tyrosine-based activation motifs (ITAM) of some cell surface receptors, for example T cell receptor (TCR)[18] and CD79a/b.[19] SHIP1 does not bind only to intracellular chains of cell surface receptor. Its SH2 domain may also interact with phosphorylated cytoplasmic proteins, such as SHC1[20] and DOK1.[21]
The regulation of signaling by SHIP1 is not dependent only on its catalytic activity. SHIP1 can also affect cell signaling pathways independently on its catalytic activity by serving as a bridge for other proteins thereby regulate protein-protein interactions.
Interactions
INPP5D has been shown to
Medicines
Poor regulation of the SHIP1 function leads to different pathologies. On the one hand, its increased activity is associated with
allosteric activator. Currently, some molecules are under development and tested as potential anti-inflammatory drug. AQX-1125 (Rosiptor) and AQX-MN100 are both in clinical trials.[32][33][13]
References
- ^ a b c ENSG00000281614 GRCh38: Ensembl release 89: ENSG00000168918, ENSG00000281614 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026288 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PMID 8643691.
- PMID 8874179.
- ^ a b "Entrez Gene: INPP5D inositol polyphosphate-5-phosphatase, 145kDa".
- PMID 9058707.
- PMID 19074735.
- S2CID 41934928.
- ^ PMID 21155837.
- PMID 19494109.
- ^ PMID 17502453.
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- PMID 15713798.
- PMID 8910587.
- S2CID 5676779.
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- ^ PMID 10822173.
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- S2CID 31471121.
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- PMID 12024011.
- PMID 10900203.
- ^ AdisInsight. "AQX-1125". Springer. Archived from the original on 15 July 2016. Retrieved 20 July 2016.
{{cite web}}: CS1 maint: bot: original URL status unknown (link) - ^ World Health Organization, International Nonproprietary Names for Pharmaceutical Substances (INN): Proposed INN: List 115 (PDF)
Further reading
- MacDonald SM, Vonakis BM (September 2002). "Association of the Src homology 2 domain-containing inositol 5' phosphatase (SHIP) to releasability in human basophils". Molecular Immunology. 38 (16–18): 1323–7. PMID 12217402.
- Lioubin MN, Algate PA, Tsai S, Carlberg K, Aebersold A, Rohrschneider LR (May 1996). "p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity". Genes & Development. 10 (9): 1084–95. PMID 8654924.
- Kavanaugh WM, Pot DA, Chin SM, Deuter-Reinhard M, Jefferson AB, Norris FA, Masiarz FR, Cousens LS, Majerus PW, Williams LT (April 1996). "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2". Current Biology. 6 (4): 438–45. S2CID 15858192.
- Drayer AL, Pesesse X, De Smedt F, Woscholski R, Parker P, Erneux C (August 1996). "Cloning and expression of a human placenta inositol 1,3,4,5-tetrakisphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase". Biochemical and Biophysical Research Communications. 225 (1): 243–9. PMID 8769125.
- Geier SJ, Algate PA, Carlberg K, Flowers D, Friedman C, Trask B, Rohrschneider LR (March 1997). "The human SHIP gene is differentially expressed in cell lineages of the bone marrow and blood". Blood. 89 (6): 1876–85. PMID 9058707.
- Odai H, Sasaki K, Iwamatsu A, Nakamoto T, Ueno H, Yamagata T, Mitani K, Yazaki Y, Hirai H (April 1997). "Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl". Blood. 89 (8): 2745–56. PMID 9108392.
- Liu L, Damen JE, Ware MD, Krystal G (April 1997). "Interleukin-3 induces the association of the inositol 5-phosphatase SHIP with SHP2". The Journal of Biological Chemistry. 272 (17): 10998–1001. PMID 9110989.
- Giuriato S, Payrastre B, Drayer AL, Plantavid M, Woscholski R, Parker P, Erneux C, Chap H (October 1997). "Tyrosine phosphorylation and relocation of SHIP are integrin-mediated in thrombin-stimulated human blood platelets". The Journal of Biological Chemistry. 272 (43): 26857–63. PMID 9341117.
- Kuroiwa A, Yamashita Y, Inui M, Yuasa T, Ono M, Nagabukuro A, Matsuda Y, Takai T (January 1998). "Association of tyrosine phosphatases SHP-1 and SHP-2, inositol 5-phosphatase SHIP with gp49B1, and chromosomal assignment of the gene". The Journal of Biological Chemistry. 273 (2): 1070–4. PMID 9422771.
- Liu Q, Shalaby F, Jones J, Bouchard D, Dumont DJ (April 1998). "The SH2-containing inositol polyphosphate 5-phosphatase, ship, is expressed during hematopoiesis and spermatogenesis". Blood. 91 (8): 2753–9. PMID 9531585.
- Zhang S, Broxmeyer HE (January 1999). "p85 subunit of PI3 kinase does not bind to human Flt3 receptor, but associates with SHP2, SHIP, and a tyrosine-phosphorylated 100-kDa protein in Flt3 ligand-stimulated hematopoietic cells". Biochemical and Biophysical Research Communications. 254 (2): 440–5. PMID 9918857.
- Mikhalap SV, Shlapatska LM, Berdova AG, Law CL, Clark EA, Sidorenko SP (May 1999). "CDw150 associates with src-homology 2-containing inositol phosphatase and modulates CD95-mediated apoptosis". Journal of Immunology. 162 (10): 5719–27. S2CID 33130860.
- Pumphrey NJ, Taylor V, Freeman S, Douglas MR, Bradfield PF, Young SP, Lord JM, Wakelam MJ, Bird IN, Salmon M, Buckley CD (April 1999). "Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31". FEBS Letters. 450 (1–2): 77–83. S2CID 31471121.
- Mason JM, Beattie BK, Liu Q, Dumont DJ, Barber DL (February 2000). "The SH2 inositol 5-phosphatase Ship1 is recruited in an SH2-dependent manner to the erythropoietin receptor". The Journal of Biological Chemistry. 275 (6): 4398–406. PMID 10660611.
- Bone H, Welham MJ (March 2000). "Shc associates with the IL-3 receptor beta subunit, SHIP and Gab2 following IL-3 stimulation. Contribution of Shc PTB and SH2 domains". Cellular Signalling. 12 (3): 183–94. PMID 10704825.
- Lemay S, Davidson D, Latour S, Veillette A (April 2000). "Dok-3, a novel adapter molecule involved in the negative regulation of immunoreceptor signaling". Molecular and Cellular Biology. 20 (8): 2743–54. PMID 10733577.
- Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF (June 2000). "CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux". The Journal of Biological Chemistry. 275 (23): 17420–7. PMID 10748054.
- Dunant NM, Wisniewski D, Strife A, Clarkson B, Resh MD (May 2000). "The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells". Cellular Signalling. 12 (5): 317–26. PMID 10822173.
External links
- Overview of all the structural information available in the PDB for UniProt: Q92835 (Human Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: Q9ES52 (Mouse Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1) at the PDBe-KB.