Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Samar Masoumi-Moghaddam
  • Afshin AminiEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101868


 hSpry;  Spry

Historical Background

Sprouty was discovered and initially described by Hacohen et al. in 1998 as an inhibitor of fibroblast growth factor (FGF)-mediated tracheal branching (hence its name) in Drosophila melanogaster (Hacohen et al. 1998). Later, they further defined it as a common antagonist of FGF and epidermal growth factor (EGF) signaling pathways (Kramer et al. 1999). Along with the discovery of the Drosophila gene, or dSpry, they performed a search of the expressed sequence tag (EST) database and identified three human homologs of dSpry which were designated hSpry1, hSpry2, and hSpry3 (Hacohen et al. 1998). The fourth mammalian homolog (Spry4) was discovered later in mice (de Maximy et al. 1999) and humans (Leeksma et al. 2002). Since then, an expanding body of evidence has continued to support the crucial role of Sprouty in the regulation of key cellular processes and biological events, mainly as a modulator of receptor tyrosine kinase (RTK) signaling...

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  1. Cabrita MA, Christofori G. Sprouty proteins, masterminds of receptor tyrosine kinase signaling. Angiogenesis. 2008;11:53–62.  https://doi.org/10.1007/s10456-008-9089-1.CrossRefPubMedPubMedCentralGoogle Scholar
  2. de Maximy AA, Nakatake Y, Moncada S, Itoh N, Thiery JP, Bellusci S. Cloning and expression pattern of a mouse homologue of drosophila sprouty in the mouse embryo. Mech Dev. 1999;81:213–6.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Ding W, Bellusci S, Shi W, Warburton D. Genomic structure and promoter characterization of the human Sprouty4 gene, a novel regulator of lung morphogenesis. Am J Physiol Lung Cell Mol Physiol. 2004;287:L52–9.  https://doi.org/10.1152/ajplung.00430.2003.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Edwin F, Anderson K, Ying C, Patel TB. Intermolecular interactions of Sprouty proteins and their implications in development and disease. Mol Pharmacol. 2009;76:679–91.  https://doi.org/10.1124/mol.109.055848.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Gross I, Bassit B, Benezra M, Licht JD. Mammalian sprouty proteins inhibit cell growth and differentiation by preventing ras activation. J Biol Chem. 2001;276:46460–8.  https://doi.org/10.1074/jbc.M108234200.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Gross I, Armant O, Benosman S, de Aguilar JL, Freund JN, Kedinger M, et al. Sprouty2 inhibits BDNF-induced signaling and modulates neuronal differentiation and survival. Cell Death Differ. 2007;14:1802–12.  https://doi.org/10.1038/sj.cdd.4402188. [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  7. Guo C, Degnin CR, Laederich MB, Lunstrum GP, Holden P, Bihlmaier J, et al. Sprouty 2 disturbs FGFR3 degradation in thanatophoric dysplasia type II: a severe form of human achondroplasia. Cell Signal. 2008;20:1471–7.  https://doi.org/10.1016/j.cellsig.2008.04.001.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Hacohen N, Kramer S, Sutherland D, Hiromi Y, Krasnow MA. Sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell. 1998;92:253–63. doi:S0092-8674(00)80919-8 [pii].PubMedPubMedCentralCrossRefGoogle Scholar
  9. Huebert RC, Li Q, Adhikari N, Charles NJ, Han X, Ezzat MK, et al. Identification and regulation of Sprouty1, a negative inhibitor of the ERK cascade, in the human heart. Physiol Genomics. 2004;18:284–9.  https://doi.org/10.1152/physiolgenomics.00098.2004.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Impagnatiello MA, Weitzer S, Gannon G, Compagni A, Cotten M, Christofori G. Mammalian sprouty-1 and -2 are membrane-anchored phosphoprotein inhibitors of growth factor signaling in endothelial cells. J Cell Biol. 2001;152:1087–98.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Ishida M, Ichihara M, Mii S, Jijiwa M, Asai N, Enomoto A, et al. Sprouty2 regulates growth and differentiation of human neuroblastoma cells through RET tyrosine kinase. Cancer Sci. 2007;98:815–21.  https://doi.org/10.1111/j.1349-7006.2007.00457.x.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Kramer S, Okabe M, Hacohen N, Krasnow MA, Hiromi Y. Sprouty: a common antagonist of FGF and EGF signaling pathways in Drosophila. Development. 1999;126:2515–25.PubMedPubMedCentralGoogle Scholar
  13. Leeksma OC, Van Achterberg TA, Tsumura Y, Toshima J, Eldering E, Kroes WG, et al. Human sprouty 4, a new ras antagonist on 5q31, interacts with the dual specificity kinase TESK1. Eur J Biochem. 2002;269:2546–56.  https://doi.org/10.1046/j.1432-1033.2002.02921.x. [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  14. Lito P, Mets BD, Kleff S, O’Reilly S, Maher VM, McCormick JJ. Evidence that sprouty 2 is necessary for sarcoma formation by H-Ras oncogene-transformed human fibroblasts. J Biol Chem. 2008;283:2002–9.  https://doi.org/10.1074/jbc.M709046200.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Mason JM, Morrison DJ, Basson MA, Licht JD. Sprouty proteins: multifaceted negative-feedback regulators of receptor tyrosine kinase signaling. Trends Cell Biol. 2006;16:45–54.  https://doi.org/10.1016/j.tcb.2005.11.004.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Masoumi-Moghaddam S, Amini A, Morris D. The developing story of Sprouty and cancer. Cancer Metastasis Rev. 2014;33:695–720.  https://doi.org/10.1007/s10555-014-9497-1.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Minowada G, Jarvis LA, Chi CL, Neubuser A, Sun X, Hacohen N, et al. Vertebrate Sprouty genes are induced by FGF signaling and can cause chondrodysplasia when overexpressed. Development. 1999;126:4465–75.PubMedPubMedCentralGoogle Scholar
  18. Ongur D, Pohlman J, Dow AL, Eisch AJ, Edwin F, Heckers S, et al. Electroconvulsive seizures stimulate glial proliferation and reduce expression of Sprouty2 within the prefrontal cortex of rats. Biol Psychiatry. 2007;62:505–12.  https://doi.org/10.1016/j.biopsych.2006.11.014.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Pillai A. Decreased expression of Sprouty2 in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder: a correlation with BDNF expression. PLoS One. 2008;3:e1784.  https://doi.org/10.1371/journal.pone.0001784.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Quigley DA, To MD, Kim IJ, Lin KK, Albertson DG, Sjolund J, et al. Network analysis of skin tumor progression identifies a rewired genetic architecture affecting inflammation and tumor susceptibility. Genome Biol. 2011;12:R5.  https://doi.org/10.1186/gb-2011-12-1-r5.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Sayed D, Rane S, Lypowy J, He M, Chen IY, Vashistha H, et al. MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol Biol Cell. 2008;19:3272–82.  https://doi.org/10.1091/mbc.E08-02-0159.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456:980–4.  https://doi.org/10.1038/nature07511.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Wong ES, Fong CW, Lim J, Yusoff P, Low BC, Langdon WY, et al. Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling. EMBO J. 2002;21:4796–808.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Zhang C, Chaturvedi D, Jaggar L, Magnuson D, Lee JM, Patel TB. Regulation of vascular smooth muscle cell proliferation and migration by human sprouty 2. Arterioscler Thromb Vasc Biol. 2005;25:533–8. doi:01.ATV.0000155461.50450.5a [pii].PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Roswell Park Cancer InstituteBuffaloUSA
  2. 2.St George HospitalUniversity of New South WalesSydneyAustralia