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Gene Review

SPRY1  -  sprouty homolog 1, antagonist of FGF...

Homo sapiens

Synonyms: Protein sprouty homolog 1, Spry-1, hSPRY1
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Disease relevance of SPRY1

  • A specific region of 37 amino acid residues in the SPRY (B30.2) domain of African green monkey TRIM5alpha determines species-specific restriction of simian immunodeficiency virus SIVmac infection [1].
  • Here we show that TRIM5alpha binds retroviral CA from detergent-stripped virions in a SPRY-dependent manner with sufficient discrimination to account for the exquisite specificity of restriction [2].

High impact information on SPRY1

  • Sprouty (Spry) inhibits signalling by receptor tyrosine kinases; however, the molecular mechanism underlying this function has not been defined [3].
  • Membrane translocation of Spry is necessary for its phosphorylation, which is essential for its inhibitor activity [3].
  • Here we show that after stimulation by growth factors Spry1 and Spry2 translocate to the plasma membrane and become phosphorylated on a conserved tyrosine [3].
  • The amino acids lining the binding surface are highly variable among the B30.2/SPRY domains, suggesting that these domains are protein-interacting modules, which recognize a specific individual partner protein rather than a consensus sequence motif [4].
  • A 13-aa "patch" in the SPRY protein domain bears a dense concentration of positively selected residues, potentially implicating it as an antiviral interface [5].

Biological context of SPRY1


Anatomical context of SPRY1

  • We compared the ability of the mammalian Spry isoforms to inhibit the Ras/ERK pathway in the context of fibroblast growth factor receptor (FGFR) signaling [11].
  • The ability to inhibit neurite outgrowth in PC-12 cells correlates with the propensity of Spry isoforms and engineered constructs to inhibit the phosphorylation of ERK1/2 [11].
  • We additionally investigated the expression of an SPRY1 alternative transcript presumed to be specific for fetal tissues and found its expression moderately well correlated with expression of the standard transcript through diverse tissues and cell lines [7].
  • In COS-1 and Swiss 3T3 cells, all Spry isoforms translocate to the plasma membrane, notably ruffles, following activation [12].
  • In unstimulated cells, the Spry proteins were distributed throughout the cytosol except for human Sprouty2 (hSpry2), which, although generally located in the cytosol, co-localized with microtubules [10].

Regulatory relationships of SPRY1


Other interactions of SPRY1

  • Co-expression of SIAH2 resulted in proteasomal degradation of Spry1, 2, and to a lesser extent Spry4 [8].
  • Spry2 inhibits FGF-dependent ERK activation and thus Spry acts as a feedback inhibitor of FGF-mediated proliferation [8].
  • SPROUTY (SPRY) and SPRED family genes encode inhibitors for receptor tyrosine kinase signaling cascades, such as those of FGF receptor family members and EGF receptor family members [15].
  • Sprouty proteins encoded by the SPRY genes act as modulators and feedback inhibitors of signalling by epidermal growth factor (EGF) and fibroblast growth factor (FGF) [7].
  • In contrast, in naive T cells, Spry1 overexpression enhanced TCR signaling, and increased proliferation and IL-2 production, while siRNA transfection again had the opposite effect, reducing IL-2 production following activation [14].

Analytical, diagnostic and therapeutic context of SPRY1


  1. A specific region of 37 amino acid residues in the SPRY (B30.2) domain of African green monkey TRIM5alpha determines species-specific restriction of simian immunodeficiency virus SIVmac infection. Nakayama, E.E., Miyoshi, H., Nagai, Y., Shioda, T. J. Virol. (2005) [Pubmed]
  2. TRIM5alpha selectively binds a restriction-sensitive retroviral capsid. Sebastian, S., Luban, J. Retrovirology (2005) [Pubmed]
  3. Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway. Hanafusa, H., Torii, S., Yasunaga, T., Nishida, E. Nat. Cell Biol. (2002) [Pubmed]
  4. Structural and functional insights into the B30.2/SPRY domain. Woo, J.S., Imm, J.H., Min, C.K., Kim, K.J., Cha, S.S., Oh, B.H. EMBO J. (2006) [Pubmed]
  5. Positive selection of primate TRIM5alpha identifies a critical species-specific retroviral restriction domain. Sawyer, S.L., Wu, L.I., Emerman, M., Malik, H.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. Identification and expression analysis of a novel splice variant of human Sprouty1 gene. Wang, L., Ji, C., Wu, H., Xu, J., Wu, Q., Dai, J., Yin, G., Ye, X., Gu, S., Xie, Y., Mao, Y. Int. J. Mol. Med. (2003) [Pubmed]
  7. Concomitant down-regulation of SPRY1 and SPRY2 in prostate carcinoma. Fritzsche, S., Kenzelmann, M., Hoffmann, M.J., Müller, M., Engers, R., Gröne, H.J., Schulz, W.A. Endocr. Relat. Cancer (2006) [Pubmed]
  8. Regulation of Sprouty2 stability by mammalian Seven-in-Absentia homolog 2. Nadeau, R.J., Toher, J.L., Yang, X., Kovalenko, D., Friesel, R. J. Cell. Biochem. (2007) [Pubmed]
  9. Assignment of SPROUTY 1 (SPRY1) gene to tammar wallaby chromosome 6 by fluorescence in situ hybridisation. Charchar, F.J., Svartman, M., Graves, J.A. Cytogenet. Cell Genet. (2000) [Pubmed]
  10. Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain. Lim, J., Wong, E.S., Ong, S.H., Yusoff, P., Low, B.C., Guy, G.R. J. Biol. Chem. (2000) [Pubmed]
  11. A Src Homology 3-binding Sequence on the C Terminus of Sprouty2 Is Necessary for Inhibition of the Ras/ERK Pathway Downstream of Fibroblast Growth Factor Receptor Stimulation. Lao, D.H., Chandramouli, S., Yusoff, P., Fong, C.W., Saw, T.Y., Tai, L.P., Yu, C.Y., Leong, H.F., Guy, G.R. J. Biol. Chem. (2006) [Pubmed]
  12. The cysteine-rich sprouty translocation domain targets mitogen-activated protein kinase inhibitory proteins to phosphatidylinositol 4,5-bisphosphate in plasma membranes. Lim, J., Yusoff, P., Wong, E.S., Chandramouli, S., Lao, D.H., Fong, C.W., Guy, G.R. Mol. Cell. Biol. (2002) [Pubmed]
  13. Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is crucial for its function. Fong, C.W., Leong, H.F., Wong, E.S., Lim, J., Yusoff, P., Guy, G.R. J. Biol. Chem. (2003) [Pubmed]
  14. Dual Effects of Sprouty1 on TCR Signaling Depending on the Differentiation State of the T Cell. Choi, H., Cho, S.Y., Schwartz, R.H., Choi, K. J. Immunol. (2006) [Pubmed]
  15. FGF signaling inhibitor, SPRY4, is evolutionarily conserved target of WNT signaling pathway in progenitor cells. Katoh, Y., Katoh, M. Int. J. Mol. Med. (2006) [Pubmed]
  16. Human placental Hofbauer cells express sprouty proteins: a possible modulating mechanism of villous branching. Anteby, E.Y., Natanson-Yaron, S., Greenfield, C., Goldman-Wohl, D., Haimov-Kochman, R., Holzer, H., Yagel, S. Placenta (2005) [Pubmed]
  17. Dynamics of the SPRY domain-containing SOCS box protein 2: Flexibility of key functional loops. Yao, S., Liu, M.S., Masters, S.L., Zhang, J.G., Babon, J.J., Nicola, N.A., Nicholson, S.E., Norton, R.S. Protein Sci. (2006) [Pubmed]
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