Gene Symbol: Spry2
Description: sprouty RTK signaling antagonist 2
Alias: sprouty2, protein sprouty homolog 2, sprouty homolog 2, spry-2
Species: mouse
Products:     Spry2

Top Publications

  1. Shim K, Minowada G, Coling D, Martin G. Sprouty2, a mouse deafness gene, regulates cell fate decisions in the auditory sensory epithelium by antagonizing FGF signaling. Dev Cell. 2005;8:553-64 pubmed
    ..Here, we report that Sprouty2, which encodes a negative regulator of signaling via receptor tyrosine kinases, is required for normal hearing in ..
  2. Mailleux A, Kelly R, Veltmaat J, De Langhe S, Zaffran S, Thiery J, et al. Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage. Development. 2005;132:2157-66 pubmed
    ..We provide support for a role of epithelial BMP4 in mediating the formation of parabronchial smooth muscle cells...
  3. Taniguchi K, Ayada T, Ichiyama K, Kohno R, Yonemitsu Y, Minami Y, et al. Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling. Biochem Biophys Res Commun. 2007;352:896-902 pubmed
    ..Physiological function of Sprouty1 and Sprouty2 has been investigated using gene targeting approaches, however to date detailed examination of Sprouty4 knockout (..
  4. Tefft D, Lee M, Smith S, Crowe D, Bellusci S, Warburton D. mSprouty2 inhibits FGF10-activated MAP kinase by differentially binding to upstream target proteins. Am J Physiol Lung Cell Mol Physiol. 2002;283:L700-6 pubmed
    Murine Sprouty2 (mSpry2) is a conserved ortholog of Drosophila Sprouty, a gene that inhibits several tyrosine kinase receptor pathways, resulting in net reduction of mitogen-activated protein (MAP) kinase activation...
  5. White A, Xu J, Yin Y, Smith C, Schmid G, Ornitz D. FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains. Development. 2006;133:1507-17 pubmed
  6. Chi C, Martinez S, Wurst W, Martin G. The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum. Development. 2003;130:2633-44 pubmed
    ..Our data show that Fgf8 is part of a complex gene regulatory network that is essential for cell survival in the mes/met. ..
  7. Lin W, Fürthauer M, Thisse B, Thisse C, Jing N, Ang S. Cloning of the mouse Sef gene and comparative analysis of its expression with Fgf8 and Spry2 during embryogenesis. Mech Dev. 2002;113:163-8 pubmed
    ..Expression of Sef is similar to that of Fgf8 and Spry2 during early embryogenesis, being prominent in the forebrain, mid-hindbrain boundary, branchial arches, somites, ..
  8. Gross I, Bassit B, Benezra M, Licht J. Mammalian sprouty proteins inhibit cell growth and differentiation by preventing ras activation. J Biol Chem. 2001;276:46460-8 pubmed
    ..In this study, we provide a functional characterization of mammalian Sprouty1 and Sprouty2. Sprouty1 and Sprouty2 inhibited events downstream of multiple receptor tyrosine kinases and regulated both cell ..
  9. Abler L, Mansour S, Sun X. Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung. Dev Dyn. 2009;238:1999-2013 pubmed publisher
    ..Our results indicate that both Fgf10 and Fgfr2 are required for a normal branching program and for proper proximal-distal patterning of the lung. ..

More Information


  1. Impagnatiello M, 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 pubmed
    ..The data indicate that mammalian Spry-1 and -2 are membrane-anchored proteins that negatively regulate angiogenesis-associated RTK signaling, possibly in a RTK-specific fashion. ..
  2. Mason J, Morrison D, Bassit B, Dimri M, Band H, Licht J, et al. Tyrosine phosphorylation of Sprouty proteins regulates their ability to inhibit growth factor signaling: a dual feedback loop. Mol Biol Cell. 2004;15:2176-88 pubmed
    ..We identified Tyr55 as a key residue for Sprouty2 phosphorylation and showed that phosphorylation was required for Sprouty2 to inhibit RTK signaling, because a ..
  3. De Langhe S, Carraro G, Warburton D, Hajihosseini M, Bellusci S. Levels of mesenchymal FGFR2 signaling modulate smooth muscle progenitor cell commitment in the lung. Dev Biol. 2006;299:52-62 pubmed
    ..Our work unravels part of the complex interactions that govern normal lung development and may be pertinent to understanding the basis of respiratory defects in Apert syndrome. ..
  4. Zhu W, Nelson C. PI3K regulates branch initiation and extension of cultured mammary epithelia via Akt and Rac1 respectively. Dev Biol. 2013;379:235-45 pubmed publisher
    ..Akt was enhanced at branch initiation sites where its negative regulator, PTEN, was blocked by signaling via Sprouty2 (SPRY2); inhibiting Akt prevented branch initiation...
  5. Caton J, Luder H, Zoupa M, Bradman M, Bluteau G, Tucker A, et al. Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors. Dev Biol. 2009;328:493-505 pubmed publisher
    ..These results demonstrate that Tbx1 is essential for the maintenance of ameloblast progenitor cells in rodent incisors and that its deletion results in the absence of enamel formation...
  6. Yin Y, Wang F, Ornitz D. Mesothelial- and epithelial-derived FGF9 have distinct functions in the regulation of lung development. Development. 2011;138:3169-77 pubmed publisher
    ..We show that FGF signaling is primarily responsible for regulating mesenchymal proliferation, whereas ?-catenin signaling is a required permissive factor for mesenchymal FGF signaling. ..
  7. Feller J, Schneider A, Schuster Gossler K, Gossler A. Noncyclic Notch activity in the presomitic mesoderm demonstrates uncoupling of somite compartmentalization and boundary formation. Genes Dev. 2008;22:2166-71 pubmed publisher
    ..Embryos expressing NICD formed up to 18 somites. Expression in the PSM of Hes7, Lfng, and Spry2 was no longer cyclic, whereas Axin2 was expressed dynamically...
  8. Klein O, Minowada G, Peterkova R, Kangas A, Yu B, Lesot H, et al. Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling. Dev Cell. 2006;11:181-90 pubmed
    ..We show that different Sprouty genes are deployed in different tissue compartments--Spry2 in epithelium and Spry4 in mesenchyme--to prevent diastema tooth formation...
  9. Nutt S, Dingwell K, Holt C, Amaya E. Xenopus Sprouty2 inhibits FGF-mediated gastrulation movements but does not affect mesoderm induction and patterning. Genes Dev. 2001;15:1152-66 pubmed
    ..We have cloned Xenopus sprouty2 and show that it is expressed in a similar pattern to known FGFs and is dependent on the FGF/Ras/MAPK pathway for ..
  10. Zhang S, Lin Y, Itäranta P, Yagi A, Vainio S. Expression of Sprouty genes 1, 2 and 4 during mouse organogenesis. Mech Dev. 2001;109:367-70 pubmed
    ..such as the semicircular canal, Rathke's pouch, nasal organs, the follicle of vibrissae and teeth, Sprouty1 and Sprouty2 are expressed in the epithelium and Sprouty4 in the mesenchyme or neuronal tissue, while in the lung Sprouties1, ..
  11. Minowada G, Miller Y. Overexpression of Sprouty 2 in mouse lung epithelium inhibits urethane-induced tumorigenesis. Am J Respir Cell Mol Biol. 2009;40:31-7 pubmed publisher
    ..These results demonstrate that Sprouty 2 overexpression inhibited both tumor initiation and subsequent tumor growth...
  12. Minowada G, Jarvis L, Chi C, Neubüser 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 pubmed
  13. Charles C, Hovorakova M, Ahn Y, Lyons D, Marangoni P, Churava S, et al. Regulation of tooth number by fine-tuning levels of receptor-tyrosine kinase signaling. Development. 2011;138:4063-73 pubmed publisher
  14. Schutzman J, Martin G. Sprouty genes function in suppression of prostate tumorigenesis. Proc Natl Acad Sci U S A. 2012;109:20023-8 pubmed publisher
    ..Here we show they function in prostate tumor suppression in the mouse. Concomitant inactivation of Spry1 and Spry2 in prostate epithelium causes ductal hyperplasia and low-grade prostatic intraepithelial neoplasia (PIN)...
  15. Metzger R, Klein O, Martin G, Krasnow M. The branching programme of mouse lung development. Nature. 2008;453:745-50 pubmed publisher
    ..We show that this hierarchical and modular programme is genetically tractable, and it is ideally suited to encoding and evolving the complex networks of the lung and other branched organs. ..
  16. Hanafusa H, Torii S, Yasunaga T, Nishida E. Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway. Nat Cell Biol. 2002;4:850-8 pubmed
    ..Here we show that after stimulation by growth factors Spry1 and Spry2 translocate to the plasma membrane and become phosphorylated on a conserved tyrosine...
  17. Taketomi T, Yoshiga D, Taniguchi K, Kobayashi T, Nonami A, Kato R, et al. Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia. Nat Neurosci. 2005;8:855-7 pubmed
    We report here that loss of the Sprouty2 gene (also known as Spry2) in mice resulted in enteric nerve hyperplasia, which led to esophageal achalasia and intestinal pseudo-obstruction...
  18. Basson M, Echevarria D, Ahn C, Sudarov A, Joyner A, Mason I, et al. Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development. Development. 2008;135:889-98 pubmed publisher
    ..FGF signaling within the embryonic mouse midbrain (mesencephalon) and cerebellum (rhombomere 1) by misexpressing sprouty2 (Spry2) from an early stage...
  19. Simrick S, Lickert H, Basson M. Sprouty genes are essential for the normal development of epibranchial ganglia in the mouse embryo. Dev Biol. 2011;358:147-55 pubmed publisher
    ..The morphology of the facial, glossopharyngeal and vagus nerves are abnormal in Spry1-/-;Spry2-/- embryos...
  20. Domyan E, Ferretti E, Throckmorton K, Mishina Y, Nicolis S, Sun X. Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2. Development. 2011;138:971-81 pubmed publisher
  21. Tefft J, Lee M, Smith S, Leinwand M, Zhao J, Bringas P, et al. Conserved function of mSpry-2, a murine homolog of Drosophila sprouty, which negatively modulates respiratory organogenesis. Curr Biol. 1999;9:219-22 pubmed
    ..These results support a striking conservation of function between the Drosophila and mammalian sprouty gene families to negatively modulate respiratory organogenesis. ..
  22. Mahoney Rogers A, Zhang J, Shim K. Sprouty1 and Sprouty2 limit both the size of the otic placode and hindbrain Wnt8a by antagonizing FGF signaling. Dev Biol. 2011;353:94-104 pubmed publisher
    ..Here we report that in Spry1, Spry2 compound mutant embryos (Spry1?/?; Spry2?/? embryos), the otic placode is increased in size...
  23. Mailleux A, Tefft D, Ndiaye D, Itoh N, Thiery J, Warburton D, et al. Evidence that SPROUTY2 functions as an inhibitor of mouse embryonic lung growth and morphogenesis. Mech Dev. 2001;102:81-94 pubmed
    ..We investigated Sprouty2 function during lung development by two different but complementary approaches...
  24. Volckaert T, Campbell A, Dill E, Li C, Minoo P, De Langhe S. Localized Fgf10 expression is not required for lung branching morphogenesis but prevents differentiation of epithelial progenitors. Development. 2013;140:3731-42 pubmed publisher
    ..Interestingly, our data presented here show that once epithelial cells are committed to the Sox2-positive airway epithelial cell fate, Fgf10 prevents ciliated cell differentiation and promotes basal cell differentiation. ..
  25. Basson M, Akbulut S, Watson Johnson J, Simon R, Carroll T, Shakya R, et al. Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Dev Cell. 2005;8:229-39 pubmed
    ..These results demonstrate the importance of negative feedback regulation of RTK signaling during kidney induction and suggest that failures in feedback control may underlie some human congenital kidney malformations. ..
  26. Lin W, Jing N, Basson M, Dierich A, Licht J, Ang S. Synergistic activity of Sef and Sprouty proteins in regulating the expression of Gbx2 in the mid-hindbrain region. Genesis. 2005;41:110-5 pubmed
    ..5. To investigate the possibility of functional synergism between Sef and Sprouty proteins, we electroporated Sprouty2(Y55A), which functions in a dominant-negative manner in tissue culture cells into the mid-hindbrain region of ..
  27. Haglund K, Schmidt M, Wong E, Guy G, Dikic I. Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor downregulation. EMBO Rep. 2005;6:635-41 pubmed
    ..One regulatory mechanism involves the binding of Cbl to Sprouty2, which sequesters Cbl away from activated epidermal growth factor receptors (EGFRs)...
  28. Klein O, Lyons D, Balooch G, Marshall G, Basson M, Peterka M, et al. An FGF signaling loop sustains the generation of differentiated progeny from stem cells in mouse incisors. Development. 2008;135:377-85 pubmed
    ..These data reveal that the generation of differentiated progeny from a particular stem cell population can be differently regulated in the embryo and adult. ..
  29. Suzuki A, Harada H, Nakamura H. Nuclear translocation of FGF8 and its implication to induce Sprouty2. Dev Growth Differ. 2012;54:463-73 pubmed publisher
    ..Furthermore, signal-peptide-deletion mutant of FGF8b mainly localized in the nuclei, and induced Sprouty2 without activating ERK in the mesencephalon...
  30. Hines E, Jones M, Verheyden J, Harvey J, Sun X. Establishment of smooth muscle and cartilage juxtaposition in the developing mouse upper airways. Proc Natl Acad Sci U S A. 2013;110:19444-9 pubmed publisher
    ..These findings together delineate the mechanisms through which a cell-autonomous disruption of one structural tissue can have widespread consequences on upper airway function. ..
  31. Nonomura K, Yamaguchi Y, Hamachi M, Koike M, Uchiyama Y, Nakazato K, et al. Local apoptosis modulates early mammalian brain development through the elimination of morphogen-producing cells. Dev Cell. 2013;27:621-34 pubmed publisher
    ..Thus, apoptosis within a specific subdomain of the ANR is required for correct temporal elimination of an FGF8-producing region within a limited developmental time window, thereby ensuring proper forebrain development. ..
  32. Chalamalasetty R, Dunty W, Biris K, Ajima R, Iacovino M, Beisaw A, et al. The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program. Nat Commun. 2011;2:390 pubmed publisher
    ..Msgn1 also indirectly regulates cyclic genes in the Fgf and Wnt pathways. Thus, Msgn1 is a central component of a transcriptional cascade that translates a spatial Wnt3a gradient into a temporal pattern of clock gene expression. ..
  33. Sharma B, Joshi S, Sassano A, Majchrzak B, Kaur S, Aggarwal P, et al. Sprouty proteins are negative regulators of interferon (IFN) signaling and IFN-inducible biological responses. J Biol Chem. 2012;287:42352-60 pubmed publisher
    ..In other studies, we found that siRNA-mediated knockdown of Spry1, Spry2, or Spry4 promotes IFN-inducible antileukemic effects in vitro and results in enhanced suppressive effects on ..
  34. Aranda S, Alvarez M, Turró S, Laguna A, De La Luna S. Sprouty2-mediated inhibition of fibroblast growth factor signaling is modulated by the protein kinase DYRK1A. Mol Cell Biol. 2008;28:5899-911 pubmed publisher
    ..We identify DYRK1A as one of the protein kinases of Sprouty2. We show that DYRK1A interacts with and regulates the phosphorylation status of Sprouty2...
  35. Wu X, Alexander P, He Y, Kikkawa M, Vogel P, McKnight S. Mammalian sprouty proteins assemble into large monodisperse particles having the properties of intracellular nanobatteries. Proc Natl Acad Sci U S A. 2005;102:14058-62 pubmed
    ..Here we show that the mammalian Sprouty2 protein contains an iron-sulfur complex that can exist in an oxidized, reduced, or nitrosylated state...
  36. Huang X, Ketova T, Fleming J, Wang H, Dey S, Litingtung Y, et al. Sonic hedgehog signaling regulates a novel epithelial progenitor domain of the hindbrain choroid plexus. Development. 2009;136:2535-43 pubmed publisher
  37. Ribes V, Stutzmann F, Bianchetti L, Guillemot F, Dolle P, Le Roux I. Combinatorial signalling controls Neurogenin2 expression at the onset of spinal neurogenesis. Dev Biol. 2008;321:470-81 pubmed publisher
    ..Our data thus support a model where signal integration at the level of a single enhancer constitutes a key mechanism to control the onset of neurogenesis. ..
  38. Jia W, Jiang S, Tang Q, Shen D, Xue B, Ning W, et al. Geranylgeranyl Diphosphate Synthase Modulates Fetal Lung Branching Morphogenesis Possibly through Controlling K-Ras Prenylation. Am J Pathol. 2016;186:1454-65 pubmed publisher
    ..Collectively, our data suggest that GGPPS is essential for maintaining fetal lung branching morphogenesis, which is possibly through regulating K-Ras prenylation. ..
  39. Deckelbaum R, Majithia A, Booker T, Henderson J, Loomis C. The homeoprotein engrailed 1 has pleiotropic functions in calvarial intramembranous bone formation and remodeling. Development. 2006;133:63-74 pubmed
    ..In summary, this study identifies EN1 as a novel modulator of calvarial osteoblast differentiation and proliferation, processes that must be exquisitely balanced to ensure proper skull vault formation. ..
  40. Yu T, Yaguchi Y, Echevarria D, Martinez S, Basson M. Sprouty genes prevent excessive FGF signalling in multiple cell types throughout development of the cerebellum. Development. 2011;138:2957-68 pubmed publisher
    ..Here, we investigated the function of sprouty genes (Spry1, Spry2 and Spry4), which encode feedback antagonists of FGF signalling, during cerebellar development in the mouse...
  41. Tang N, Marshall W, McMahon M, Metzger R, Martin G. Control of mitotic spindle angle by the RAS-regulated ERK1/2 pathway determines lung tube shape. Science. 2011;333:342-345 pubmed publisher
  42. Unbekandt M, del Moral P, Sala F, Bellusci S, Warburton D, Fleury V. Tracheal occlusion increases the rate of epithelial branching of embryonic mouse lung via the FGF10-FGFR2b-Sprouty2 pathway. Mech Dev. 2008;125:314-24 pubmed
    ..Analysis by RT-PCR showed that Fgf10, Vegf, Sprouty2 and Shh mRNA expressions were affected by the change of intraluminal pressure after 48h of culture, suggesting ..
  43. Sylvestersen K, Herrera P, Serup P, Rescan C. Fgf9 signalling stimulates Spred and Sprouty expression in embryonic mouse pancreas mesenchyme. Gene Expr Patterns. 2011;11:105-11 pubmed publisher
    ..of the Spred and Sprouty families are expressed in embryonic mouse pancreas and find Spred1 and -2 as well as Spry2 and -4 to be predominantly expressed in pancreatic mesenchyme...
  44. Chen Z, Huang J, Liu Y, Dattilo L, Huh S, Ornitz D, et al. FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands. Development. 2014;141:2691-701 pubmed publisher
  45. Shojaee S, Caeser R, Buchner M, Park E, Swaminathan S, Hurtz C, et al. Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia. Cancer Cell. 2015;28:114-28 pubmed publisher
    ..Studying negative feedback regulation of Erk in genetic experiments at three different levels, we found that Spry2, Dusp6, and Etv5 were essential for oncogenic transformation in mouse models for pre-B acute lymphoblastic ..
  46. WIETECHA M, Chen L, Ranzer M, Anderson K, Ying C, Patel T, et al. Sprouty2 downregulates angiogenesis during mouse skin wound healing. Am J Physiol Heart Circ Physiol. 2011;300:H459-67 pubmed publisher
    ..To examine the role of Spry2 in the regulation of angiogenesis during wound repair, we used a model of murine dermal wound healing...
  47. Hausott B, Vallant N, Auer M, Yang L, Dai F, Brand Saberi B, et al. Sprouty2 down-regulation promotes axon growth by adult sensory neurons. Mol Cell Neurosci. 2009;42:328-40 pubmed publisher
    ..b>Sprouty2 revealed the highest expression level in DRG neurons...
  48. Biyashev D, Veliceasa D, Topczewski J, Topczewska J, Mizgirev I, Vinokour E, et al. miR-27b controls venous specification and tip cell fate. Blood. 2012;119:2679-87 pubmed publisher
    ..We have identified its targets, a Notch ligand Delta-like ligand 4 (Dll4) and Sprouty homologue 2 (Spry2). miR-27b knockdown in zebrafish and mouse tissues severely impaired vessel sprouting and filopodia formation...
  49. Aggarwal V, Carpenter C, Freyer L, Liao J, Petti M, Morrow B. Mesodermal Tbx1 is required for patterning the proximal mandible in mice. Dev Biol. 2010;344:669-81 pubmed publisher
    ..5. This occurs without significant changes in cell proliferation or apoptosis at the same stage. Our results elucidate a new function for the non-neural crest core mesoderm and specifically, mesodermal Tbx1, in shaping the lower jaw. ..
  50. Chandramouli S, Yu C, Yusoff P, Lao D, Leong H, Mizuno K, et al. Tesk1 interacts with Spry2 to abrogate its inhibition of ERK phosphorylation downstream of receptor tyrosine kinase signaling. J Biol Chem. 2008;283:1679-91 pubmed
    ..In this study, we have identified Tesk1 (testicular protein kinase 1) as a novel regulator of Spry2 function. Endogenous Tesk1 and Spry2 exist in a complex in cell lines and mouse tissues...
  51. Deckelbaum R, Holmes G, Zhao Z, Tong C, Basilico C, Loomis C. Regulation of cranial morphogenesis and cell fate at the neural crest-mesoderm boundary by engrailed 1. Development. 2012;139:1346-58 pubmed publisher
  52. Peier M, Walpen T, Christofori G, Battegay E, Humar R. Sprouty2 expression controls endothelial monolayer integrity and quiescence. Angiogenesis. 2013;16:455-68 pubmed publisher
    ..Here we identify the fibroblast growth factor (FGF) antagonist Sprouty2 (Spry2) as a key player in mediating endothelial quiescence and barrier integrity in mouse aortic endothelial ..
  53. Zhang J, Wright K, Mahoney Rogers A, Barrett M, Shim K. Compensatory regulation of the size of the inner ear in response to excess induction of otic progenitors by fibroblast growth factor signaling. Dev Dyn. 2014;243:1317-27 pubmed publisher
    ..Here, we examined the size of the otic placode and cup by combinatorial inactivation of the Sprouty1 and Sprouty2 genes...