Angiogenesis

, Volume 11, Issue 1, pp 53–62 | Cite as

Sprouty proteins, masterminds of receptor tyrosine kinase signaling

Original paper

Abstract

Angiogenesis relies on endothelial cells properly processing signals from growth factors provided in both an autocrine and a paracrine manner. These mitogens bind to their cognate receptor tyrosine kinases (RTKs) on the cell surface, thereby activating a myriad of complex intracellular signaling pathways whose outputs include cell growth, migration, and morphogenesis. Understanding how these cascades are precisely controlled will provide insight into physiological and pathological angiogenesis. The Sprouty (Spry) family of proteins is a highly conserved group of negative feedback loop modulators of growth factor-mediated mitogen-activated protein kinase (MAPK) activation originally described in Drosophila. There are four mammalian orthologs (Spry1-4) whose modulation of RTK-induced signaling pathways is growth factor- and cell context-dependant. Endothelial cells are a group of highly differentiated cell types necessary for defining the mammalian vasculature. These cells respond to a plethora of growth factors and express all four Spry isoforms, thus highlighting the complexity that is required to form and maintain vessels in mammals. This review describes Spry functions in the context of endothelial biology and angiogenesis, and provides an update on Spry-interacting proteins and Spry mechanisms of action.

Keywords

EGF Endothelial cell ERK FGF Growth factors MAPK Receptor tyrosine kinase Sprouty Spred VEGF 

Abbreviations

Ang

Angiopoietin

c-Cbl

Cellular homologue of Casitas B-lineage lymphoma proto-oncogene product

EGF

Epidermal growth factor

EGFR

EGF receptor

eNOS

Endothelial nitric oxide synthase

ERK

Extracellular signal-regulated kinase

FGF

Fibroblast growth factor

FGFR

FGF receptor

GDNF

Glial-derived neurotrophic factor

Grb2

Growth factor receptor-bound protein 2

HMVEC

Human microvascular endothelial cell

Hrs

Hepatocyte growth factor-regulated tyrosine kinase substrate

HUVEC

Human umbilical vein endothelial cell

MAPK

Mitogen-activated protein kinase

MEK

MAPK and ERK kinase

Mnk1

Mitogen-activated protein kinase-interacting kinase 1

PDGF

Platelet-derived growth factor

PKC

Protein kinase C

PLC

Phospholipase C

PP2A

Protein phosphatase 2A

RBD

Raf1-binding domain

RTK

Receptor tyrosine kinase

Shp2

SH2-domain-containing protein tyrosine phosphatase 2

SIAH2

Seven-in-Absentia Homolog 2

SMC

Smooth muscle cell

Sos1

Son of Sevenless 1

Spry

Sprouty

Spred

Spry-related proteins with Enabled/vasodilator-stimulated phosphoprotein homology 1 domain

SPR

Spry-related domain

VEGF

Vascular endothelial growth factor

VEGFR

VEGF receptor

References

  1. 1.
    Gschwind A, Fischer OM, Ullrich A (2004) The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer 4:361–370PubMedCrossRefGoogle Scholar
  2. 2.
    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70PubMedCrossRefGoogle Scholar
  3. 3.
    Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936PubMedCrossRefGoogle Scholar
  4. 4.
    Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364PubMedCrossRefGoogle Scholar
  5. 5.
    Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211–225PubMedCrossRefGoogle Scholar
  6. 6.
    Dor Y, Djonov V, Keshet E (2003) Making vascular networks in the adult: branching morphogenesis without a roadmap. Trends Cell Biol 13:131–136PubMedCrossRefGoogle Scholar
  7. 7.
    Lu P, Sternlicht MD, Werb Z (2006) Comparative mechanisms of branching morphogenesis in diverse systems. J Mammary Gland Biol Neoplasia 11:213–228PubMedCrossRefGoogle Scholar
  8. 8.
    Adams RH, Alitalo K (2007) Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8:464–478PubMedCrossRefGoogle Scholar
  9. 9.
    Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438:967–974PubMedCrossRefGoogle Scholar
  10. 10.
    Dikic I, Giordano S (2003) Negative receptor signalling. Curr Opin Cell Biol 15:128–135PubMedCrossRefGoogle Scholar
  11. 11.
    McKay MM, Morrison DK (2007) Integrating signals from RTKs to ERK/MAPK. Oncogene 26:3113–3121PubMedCrossRefGoogle Scholar
  12. 12.
    Amit I, Citri A, Shay T et al (2007) A module of negative feedback regulators defines growth factor signaling. Nat Genet 39:503–512PubMedCrossRefGoogle Scholar
  13. 13.
    Hacohen N, Kramer S, Sutherland D et al (1998) sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell 92:253–263PubMedCrossRefGoogle Scholar
  14. 14.
    Bundschu K, Walter U, Schuh K (2006) The VASP-Spred-Sprouty domain puzzle. J Biol Chem 281:36477–36481PubMedCrossRefGoogle Scholar
  15. 15.
    Cabrita MA, Christofori G (2003) Sprouty proteins: antagonists of endothelial cell signaling and more. Thromb Haemost 90:586–590PubMedGoogle Scholar
  16. 16.
    Guy GR, Wong ES, Yusoff P et al (2003) Sprouty: how does the branch manager work? J Cell Sci 16:3061–3068CrossRefGoogle Scholar
  17. 17.
    Kim HJ, Bar-Sagi D (2004) Modulation of signalling by Sprouty: a developing story. Nat Rev Mol Cell Biol 5:441–450PubMedCrossRefGoogle Scholar
  18. 18.
    Mason JM, Morrison DJ, Basson MA et al (2006) Sprouty proteins: multifaceted negative-feedback regulators of receptor tyrosine kinase signaling. Trends Cell Biol 16:45–54PubMedCrossRefGoogle Scholar
  19. 19.
    Bundschu K, Walter U, Schuh K (2007) Getting a first clue about SPRED functions. Bioessays 29:897–907PubMedCrossRefGoogle Scholar
  20. 20.
    Leeksma OC, Van Achterberg TA, Tsumura Y et al (2002) Human sprouty 4, a new ras antagonist on 5q31, interacts with the dual specificity kinase TESK1. Eur J Biochem 269:2546–2556PubMedCrossRefGoogle Scholar
  21. 21.
    Minowada G, Jarvis LA, Chi CL et al (1999) Vertebrate Sprouty genes are induced by FGF signaling and can cause chondrodysplasia when overexpressed. Development 126:4465–4475PubMedGoogle Scholar
  22. 22.
    Gross I, Bassit B, Benezra M et al (2001) Mammalian sprouty proteins inhibit cell growth and differentiation by preventing ras activation. J Biol Chem 276:46460–46468PubMedCrossRefGoogle Scholar
  23. 23.
    Impagnatiello MA, Weitzer S, Gannon G et al (2001) Mammalian sprouty-1 and -2 are membrane-anchored phosphoprotein inhibitors of growth factor signaling in endothelial cells. J Cell Biol 152:1087–1098PubMedCrossRefGoogle Scholar
  24. 24.
    Sasaki A, Taketomi T, Wakioka T et al (2001) Identification of a dominant negative mutant of Sprouty that potentiates fibroblast growth factor- but not epidermal growth factor-induced ERK activation. J Biol Chem 276:36804–36808PubMedCrossRefGoogle Scholar
  25. 25.
    Lim J, Wong ES, Ong SH et al (2000) Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain. J Biol Chem 275:32837–32845PubMedCrossRefGoogle Scholar
  26. 26.
    Yigzaw Y, Cartin L, Pierre S et al (2001) The C terminus of sprouty is important for modulation of cellular migration and proliferation. J Biol Chem 276:22742–22747PubMedCrossRefGoogle Scholar
  27. 27.
    Basson MA, Akbulut S, Watson-Johnson J et al (2005) Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Dev Cell 8:229–239PubMedCrossRefGoogle Scholar
  28. 28.
    Gross I, Armant O, Benosman S et al (2007) Sprouty2 inhibits BDNF-induced signaling and modulates neuronal differentiation and survival. Cell Death Differ 14:1802–1812PubMedCrossRefGoogle Scholar
  29. 29.
    Lee CC, Putnam AJ, Miranti CK et al (2004) Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis. Oncogene 23:5193–5202PubMedCrossRefGoogle Scholar
  30. 30.
    Choi H, Cho SY, Schwartz RH et al (2006) Dual effects of Sprouty1 on TCR signaling depending on the differentiation state of the T cell. J Immunol 176:6034–6045PubMedGoogle Scholar
  31. 31.
    Glienke J, Schmitt AO, Pilarsky C et al (2000) Differential gene expression by endothelial cells in distinct angiogenic states. Eur J Biochem 267:2820–2830PubMedCrossRefGoogle Scholar
  32. 32.
    Bell SE, Mavila A, Salazar R et al (2001) Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling. J Cell Sci 114:2755–2773PubMedGoogle Scholar
  33. 33.
    Jones N, Iljin K, Dumont DJ et al (2001) Tie receptors: new modulators of angiogenic and lymphangiogenic responses. Nat Rev Mol Cell Biol 2:257–267PubMedCrossRefGoogle Scholar
  34. 34.
    Chi JT, Chang HY, Haraldsen G et al (2003) Endothelial cell diversity revealed by global expression profiling. Proc Natl Acad Sci U S A 100:10623–10628PubMedCrossRefGoogle Scholar
  35. 35.
    Antoine M, Wirz W, Tag CG et al (2005) Expression pattern of fibroblast growth factors (FGFs), their receptors and antagonists in primary endothelial cells and vascular smooth muscle cells. Growth Factors 23:87–95PubMedCrossRefGoogle Scholar
  36. 36.
    Paik JH, Kollipara R, Chu G et al (2007) FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 128:309–323PubMedCrossRefGoogle Scholar
  37. 37.
    Dejana E, Taddei A, Randi AM (2007) Foxs and Ets in the transcriptional regulation of endothelial cell differentiation and angiogenesis. Biochim Biophys Acta 1775:298–312PubMedGoogle Scholar
  38. 38.
    Ding W, Bellusci S, Shi W et al (2003) Functional analysis of the human Sprouty2 gene promoter. Gene 322:175–185PubMedCrossRefGoogle Scholar
  39. 39.
    Lee SH, Schloss DJ, Jarvis L et al (2001) Inhibition of angiogenesis by a mouse sprouty protein. J Biol Chem 276:4128–4133PubMedCrossRefGoogle Scholar
  40. 40.
    Christofori G (2003) Split personalities: the agonistic antagonist Sprouty. Nat Cell Biol 5:377–379PubMedCrossRefGoogle Scholar
  41. 41.
    Cabrita MA, Jaggi F, Widjaja SP et al (2006) A functional interaction between sprouty proteins and caveolin-1. J Biol Chem 281:29201–2912PubMedCrossRefGoogle Scholar
  42. 42.
    Lao DH, Chandramouli S, Yusoff P et al (2006) 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. J Biol Chem 281:29993–30000PubMedCrossRefGoogle Scholar
  43. 43.
    Ozaki K, Miyazaki S, Tanimura S et al (2005) Efficient suppression of FGF-2-induced ERK activation by the cooperative interaction among mammalian Sprouty isoforms. J Cell Sci 118:5861–5871PubMedCrossRefGoogle Scholar
  44. 44.
    Egan JE, Hall AB, Yatsula BA et al (2002) The bimodal regulation of epidermal growth factor signaling by human Sprouty proteins. Proc Natl Acad Sci U S A 99:6041–6046PubMedCrossRefGoogle Scholar
  45. 45.
    Fong CW, Leong HF, Wong ES et al (2003) Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is crucial for its function. J Biol Chem 278:33456–33464PubMedCrossRefGoogle Scholar
  46. 46.
    Rubin C, Litvak V, Medvedovsky H et al (2003) Sprouty fine-tunes EGF signaling through interlinked positive and negative feedback loops. Curr Biol 13:297–307PubMedCrossRefGoogle Scholar
  47. 47.
    Schmelzle K, Kane S, Gridley S et al (2006) Temporal dynamics of tyrosine phosphorylation in insulin signaling. Diabetes 55:2171–2179PubMedCrossRefGoogle Scholar
  48. 48.
    Mason JM, Morrison DJ, Bassit B et al (2004) Tyrosine phosphorylation of Sprouty proteins regulates their ability to inhibit growth factor signaling: a dual feedback loop. Mol Biol Cell 15:2176–2188PubMedCrossRefGoogle Scholar
  49. 49.
    Hanafusa H, Torii S, Yasunaga T et al (2002) Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway. Nat Cell Biol 4:850–858PubMedCrossRefGoogle Scholar
  50. 50.
    Hanafusa H, Torii S, Yasunaga T et al (2004) Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty. J Biol Chem 279:22992–22995PubMedCrossRefGoogle Scholar
  51. 51.
    Jarvis LA, Toering SJ, Simon MA et al (2006) Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases. Development 133:1133–1142PubMedCrossRefGoogle Scholar
  52. 52.
    Li X, Brunton VG, Burgar HR et al (2004) FRS2-dependent SRC activation is required for fibroblast growth factor receptor-induced phosphorylation of Sprouty and suppression of ERK activity. J Cell Sci 117:6007–6017PubMedCrossRefGoogle Scholar
  53. 53.
    Presta M, Dell’Era P, Mitola S et al (2005) Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 16:159–178PubMedCrossRefGoogle Scholar
  54. 54.
    Casci T, Vinos J, Freeman M (1999) Sprouty, an intracellular inhibitor of Ras signaling. Cell 96:655–665PubMedCrossRefGoogle Scholar
  55. 55.
    Martinez N, Garcia-Dominguez CA, Domingo B et al (2007) Sprouty2 binds Grb2 at two different proline-rich regions, and the mechanism of ERK inhibition is independent of this interaction. Cell Signal 19:2277–2285PubMedCrossRefGoogle Scholar
  56. 56.
    Rubin C, Zwang Y, Vaisman N et al (2005) Phosphorylation of carboxyl-terminal tyrosines modulates the specificity of Sprouty-2 inhibition of different signaling pathways. J Biol Chem 280:9735–9744PubMedCrossRefGoogle Scholar
  57. 57.
    Lao DH, Yusoff P, Chandramouli S et al (2007) Direct binding of PP2A to Sprouty2 and phosphorylation changes are a prerequisite for ERK inhibition downstream of fibroblast growth factor receptor stimulation. J Biol Chem 282:9117–9126PubMedCrossRefGoogle Scholar
  58. 58.
    Amin DN, Hida K, Bielenberg DR et al (2006) Tumor endothelial cells express epidermal growth factor receptor (EGFR) but not ErbB3 and are responsive to EGF and to EGFR kinase inhibitors. Cancer Res 66:2173–2180PubMedCrossRefGoogle Scholar
  59. 59.
    Sini P, Wyder L, Schnell C et al (2005) The antitumor and antiangiogenic activity of vascular endothelial growth factor receptor inhibition is potentiated by ErbB1 blockade. Clin Cancer Res 11:4521–4532PubMedCrossRefGoogle Scholar
  60. 60.
    van Cruijsen H, Giaccone G, Hoekman K (2005) Epidermal growth factor receptor and angiogenesis: Opportunities for combined anticancer strategies. Int J Cancer 117:883–888PubMedCrossRefGoogle Scholar
  61. 61.
    Wong ES, Fong CW, Lim J et al (2002) Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling. EMBO J 21:4796–4808PubMedCrossRefGoogle Scholar
  62. 62.
    Wong ES, Lim J, Low BC et al (2001) Evidence for direct interaction between Sprouty and Cbl. J Biol Chem 276:5866–5875PubMedCrossRefGoogle Scholar
  63. 63.
    Haglund K, Schmidt MH, Wong ES et al (2005) Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor downregulation. EMBO Rep 6:635–641PubMedCrossRefGoogle Scholar
  64. 64.
    Kim HJ, Taylor LJ, Bar-Sagi D (2007) Spatial regulation of EGFR signaling by Sprouty2. Curr Biol 17:455–461PubMedCrossRefGoogle Scholar
  65. 65.
    Coultas L, Chawengsaksophak K, Rossant J (2005) Endothelial cells and VEGF in vascular development. Nature 438:937–945PubMedCrossRefGoogle Scholar
  66. 66.
    Takahashi T, Yamaguchi S, Chida K et al (2001) A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO J 20:2768–2778PubMedCrossRefGoogle Scholar
  67. 67.
    Sasaki A, Taketomi T, Kato R et al (2003) Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1. Nat Cell Biol 5:427–432PubMedCrossRefGoogle Scholar
  68. 68.
    Parton RG, Simons K (2007) The multiple faces of caveolae. Nat Rev Mol Cell Biol 8:185–194PubMedCrossRefGoogle Scholar
  69. 69.
    Bauer PM, Yu J, Chen Y et al (2005) Endothelial-specific expression of caveolin-1 impairs microvascular permeability and angiogenesis. Proc Natl Acad Sci U S A 102:204–209PubMedCrossRefGoogle Scholar
  70. 70.
    Lin MI, Yu J, Murata T et al (2007) Caveolin-1-deficient mice have increased tumor microvascular permeability, angiogenesis, and growth. Cancer Res 67:2849–2856PubMedCrossRefGoogle Scholar
  71. 71.
    Liu J, Wang XB, Park DS et al (2002) Caveolin-1 expression enhances endothelial capillary tubule formation. J Biol Chem 277:10661–10668PubMedCrossRefGoogle Scholar
  72. 72.
    Woodman SE, Ashton AW, Schubert W et al (2003) Caveolin-1 knockout mice show an impaired angiogenic response to exogenous stimuli. Am J Pathol 162:2059–2068PubMedGoogle Scholar
  73. 73.
    Galbiati F, Volonte D, Engelman JA et al (1998) Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade. EMBO J 17:6633–6648PubMedCrossRefGoogle Scholar
  74. 74.
    Kajita M, Ikeda W, Tamaru Y et al (2007) Regulation of platelet-derived growth factor-induced Ras signaling by poliovirus receptor Necl-5 and negative growth regulator Sprouty2. Genes Cells 12:345–357PubMedCrossRefGoogle Scholar
  75. 75.
    Sakisaka T, Ikeda W, Ogita H et al (2007) The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors. Curr Opin Cell Biol 19:593–602PubMedCrossRefGoogle Scholar
  76. 76.
    Couderc T, Barzu T, Horaud F et al (1990) Poliovirus permissivity and specific receptor expression on human endothelial cells. Virology 174:95–102PubMedCrossRefGoogle Scholar
  77. 77.
    Chandramouli S, Yu CY, Yusoff P et al (2008) Tesk1 interacts with sprouty2 to abrogate its inhibition of ERK phosphorylation downstream of receptor tyrosine kinase signaling. J Biol Chem 283:1679–1691PubMedCrossRefGoogle Scholar
  78. 78.
    Tsumura Y, Toshima J, Leeksma OC et al (2005) Sprouty-4 negatively regulates cell spreading by inhibiting the kinase activity of testicular protein kinase. Biochem J 387:627–637PubMedCrossRefGoogle Scholar
  79. 79.
    Ozaki K, Kadomoto R, Asato K et al (2001) ERK pathway positively regulates the expression of Sprouty genes. Biochem Biophys Res Commun 285:1084–1088PubMedCrossRefGoogle Scholar
  80. 80.
    Hall AB, Jura N, DaSilva J et al (2003) hSpry2 is targeted to the ubiquitin-dependent proteasome pathway by c-Cbl. Curr Biol 13:308–314PubMedCrossRefGoogle Scholar
  81. 81.
    Rubin C, Gur G, Yarden Y (2005) Negative regulation of receptor tyrosine kinases: unexpected links to c-Cbl and receptor ubiquitylation. Cell Res 15:66–71PubMedCrossRefGoogle Scholar
  82. 82.
    DaSilva J, Xu L, Kim HJ et al (2006) Regulation of sprouty stability by Mnk1-dependent phosphorylation. Mol Cell Biol 26:1898–1907PubMedCrossRefGoogle Scholar
  83. 83.
    Ding W, Shi W, Bellusci S et al (2007) Sprouty2 downregulation plays a pivotal role in mediating crosstalk between TGF-beta1 signaling and EGF as well as FGF receptor tyrosine kinase-ERK pathways in mesenchymal cells. J Cell Physiol 212:796–806PubMedCrossRefGoogle Scholar
  84. 84.
    Nadeau RJ, Toher JL, Yang X et al (2007) Regulation of Sprouty2 stability by mammalian Seven-in-Absentia homolog 2. J Cell Biochem 100:151–160PubMedCrossRefGoogle Scholar
  85. 85.
    Jain RK (2003) Molecular regulation of vessel maturation. Nat Med 9:685–693PubMedCrossRefGoogle Scholar
  86. 86.
    Wu X, Alexander PB, He Y et al (2005) Mammalian sprouty proteins assemble into large monodisperse particles having the properties of intracellular nanobatteries. Proc Natl Acad Sci U S A 102:14058–14062PubMedCrossRefGoogle Scholar
  87. 87.
    Wingrove JA, O’Farrell PH (1999) Nitric oxide contributes to behavioral, cellular, and developmental responses to low oxygen in Drosophila. Cell 98:105–114PubMedCrossRefGoogle Scholar
  88. 88.
    Ying L, Hofseth LJ (2007) An emerging role for endothelial nitric oxide synthase in chronic inflammation and cancer. Cancer Res 67:1407–1410PubMedCrossRefGoogle Scholar
  89. 89.
    Minshall RD, Sessa WC, Stan RV et al (2003) Caveolin regulation of endothelial function. Am J Physiol Lung Cell Mol Physiol 285:L1179–L1183PubMedGoogle Scholar
  90. 90.
    Basson MA, Watson-Johnson J, Shakya R et al (2006) Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1. Dev Biol 299:466–477PubMedCrossRefGoogle Scholar
  91. 91.
    Shim K, Minowada G, Coling DE et al (2005) Sprouty2, a mouse deafness gene, regulates cell fate decisions in the auditory sensory epithelium by antagonizing FGF signaling. Dev Cell 8:553–564PubMedCrossRefGoogle Scholar
  92. 92.
    Taketomi T, Yoshiga D, Taniguchi K et al (2005) Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia. Nat Neurosci 8:855–857PubMedGoogle Scholar
  93. 93.
    Klein OD, Minowada G, Peterkova R et al (2006) Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling. Dev Cell 11:181–190PubMedCrossRefGoogle Scholar
  94. 94.
    Taniguchi K, Ayada T, Ichiyama K et al (2007) Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling. Biochem Biophys Res Commun 352:896–902PubMedCrossRefGoogle Scholar
  95. 95.
    Sivak JM, Petersen LF, Amaya E (2005) FGF signal interpretation is directed by Sprouty and Spred proteins during mesoderm formation. Dev Cell 8:689–701PubMedCrossRefGoogle Scholar
  96. 96.
    Taniguchi K, Kohno R, Ayada T et al (2007) Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling. Mol Cell Biol 27:4541–4550PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Institute of Biochemistry and Genetics, Department of BiomedicineUniversity of BaselBaselSwitzerland

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