Gene Symbol: SPRY2
Description: sprouty RTK signaling antagonist 2
Alias: IGAN3, hSPRY2, protein sprouty homolog 2
Species: human
Products:     SPRY2

Top Publications

  1. Kim H, Taylor L, Bar Sagi D. Spatial regulation of EGFR signaling by Sprouty2. Curr Biol. 2007;17:455-61 pubmed
    ..Here we show that human Sprouty 2 (hSpry2), a protein that has been implicated in the negative regulation of receptor tyrosine kinase (RTK) signaling [1], ..
  2. Sweet S, Mardakheh F, Ryan K, Langton A, Heath J, Cooper H. Targeted online liquid chromatography electron capture dissociation mass spectrometry for the localization of sites of in vivo phosphorylation in human Sprouty2. Anal Chem. 2008;80:6650-7 pubmed publisher
    ..The approach was applied to phosphorylation analysis of human Sprouty2, a regulator of receptor tyrosine kinase signaling. Fifteen sites of phosphorylation were identified, 11 of which are novel. ..
  3. Lee C, Putnam A, Miranti C, Gustafson M, Wang L, Vande Woude G, et al. Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis. Oncogene. 2004;23:5193-202 pubmed
    ..Several negative regulators of Met signaling have been identified. Here we report that human Spry2 is induced by HGF/SF and negatively regulates HGF/SF-Met signaling...
  4. Chi L, Zhang S, Lin Y, Prunskaite Hyyryläinen R, Vuolteenaho R, Itäranta P, et al. Sprouty proteins regulate ureteric branching by coordinating reciprocal epithelial Wnt11, mesenchymal Gdnf and stromal Fgf7 signalling during kidney development. Development. 2004;131:3345-56 pubmed
    ..We have addressed the function of sprouty proteins in vivo by targeted expression of human sprouty 2 (SPRY2) in the ureteric bud, which normally expresses inductive signals and mouse sprouty 2 (Spry2)...
  5. Ng C, Jackson R, Buschdorf J, Sun Q, Guy G, Sivaraman J. Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates. EMBO J. 2008;27:804-16 pubmed publisher
  6. Lim J, Yusoff P, Wong E, Chandramouli S, Lao D, Fong C, et al. The cysteine-rich sprouty translocation domain targets mitogen-activated protein kinase inhibitory proteins to phosphatidylinositol 4,5-bisphosphate in plasma membranes. Mol Cell Biol. 2002;22:7953-66 pubmed
    ..Alignment of the Spry and Spred proteins led us to identify a translocation-defective point mutant, hSpry2 D252...
  7. Fong C, Chua M, McKie A, Ling S, Mason V, Li R, et al. Sprouty 2, an inhibitor of mitogen-activated protein kinase signaling, is down-regulated in hepatocellular carcinoma. Cancer Res. 2006;66:2048-58 pubmed
    ..is enhanced via multiple hepatocarcinogenic factors, we observed a consistent reduced expression of the sprouty 2 (Spry2) transcript and protein in malignant hepatocytes compared with normal or cirrhotic hepatocytes...
  8. McKie A, Douglas D, Olijslagers S, Graham J, Omar M, Heer R, et al. Epigenetic inactivation of the human sprouty2 (hSPRY2) homologue in prostate cancer. Oncogene. 2005;24:2166-74 pubmed
    ..041). A large CpG island is associated with hSPRY2, and extensive hypermethylation of this CpG island was observed in 76-82% of high-grade CaP, while control BPH ..
  9. Faratian D, Sims A, Mullen P, Kay C, Um I, Langdon S, et al. Sprouty 2 is an independent prognostic factor in breast cancer and may be useful in stratifying patients for trastuzumab therapy. PLoS ONE. 2011;6:e23772 pubmed publisher
    ..Changes in expression of Spry2 and feedback inhibition on trastuzumab resistance were studied in SKBr3 and BT474 breast carcinoma cell lines ..

More Information


  1. 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...
  2. Lao D, Chandramouli S, Yusoff P, Fong C, Saw T, Tai L, et al. 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. 2006;281:29993-30000 pubmed
    ..b>Spry2 is considerably more inhibitory than Spry1 or Spry4, and this correlates with the binding to Grb2 via a C-terminal ..
  3. Frank M, Dawson D, Bensinger S, Hong J, Knosp W, Xu L, et al. Expression of sprouty2 inhibits B-cell proliferation and is epigenetically silenced in mouse and human B-cell lymphomas. Blood. 2009;113:2478-87 pubmed publisher
    ..B-cell tumors to discover tumor-associated epigenetic changes, and identified hypermethylation of sprouty2 (Spry2)...
  4. Lito P, Mets B, Kleff S, O Reilly S, Maher V, McCormick J. Evidence that sprouty 2 is necessary for sarcoma formation by H-Ras oncogene-transformed human fibroblasts. J Biol Chem. 2008;283:2002-9 pubmed
    Sprouty 2 (Spry2) acts as an inhibitor of receptor tyrosine kinase signaling in various cellular contexts. Interestingly, Spry2 also prevents the c-Cbl-induced degradation of epidermal growth factor receptor (EGFR)...
  5. Sutterlüty H, Mayer C, Setinek U, Attems J, Ovtcharov S, Mikula M, et al. Down-regulation of Sprouty2 in non-small cell lung cancer contributes to tumor malignancy via extracellular signal-regulated kinase pathway-dependent and -independent mechanisms. Mol Cancer Res. 2007;5:509-20 pubmed
    ..In this study, we show a consistently lowered Spry2 expression in NSCLC when compared with the corresponding normal lung epithelium...
  6. Nadeau R, Toher J, Yang X, Kovalenko D, Friesel R. Regulation of Sprouty2 stability by mammalian Seven-in-Absentia homolog 2. J Cell Biochem. 2007;100:151-60 pubmed
    ..b>Spry2 inhibits FGF-dependent ERK activation and thus Spry acts as a feedback inhibitor of FGF-mediated proliferation...
  7. Hacohen N, Kramer S, Sutherland D, Hiromi Y, Krasnow M. sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell. 1998;92:253-63 pubmed
    ..sprouty encodes a novel cysteine-rich protein that defines a new family of putative signaling molecules that may similarly function as FGF antagonists in vertebrate development. ..
  8. Sasaki A, Taketomi T, Kato R, Saeki K, Nonami A, Sasaki M, et al. Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1. Nat Cell Biol. 2003;5:427-32 pubmed
    ..Our results show that receptor tyrosine kinases use distinct pathways for Raf and ERK activation and that Sprouty4 differentially regulates these pathways. ..
  9. Hanafusa H, Torii S, Yasunaga T, Matsumoto K, Nishida E. Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty. J Biol Chem. 2004;279:22992-5 pubmed
    ..These findings suggest that Shp2 acts as a positive regulator in RTK signaling by dephosphorylating and inactivating Spry. ..
  10. Lee S, Ho C, Roy R, Kosinski C, Patil M, Tward A, et al. Integration of genomic analysis and in vivo transfection to identify sprouty 2 as a candidate tumor suppressor in liver cancer. Hepatology. 2008;47:1200-10 pubmed publisher
    ..Among these down-regulated genes is Sprouty2 (Spry2), a known inhibitor of receptor tyrosine kinases...
  11. Hall A, Jura N, DaSilva J, Jang Y, Gong D, Bar Sagi D. hSpry2 is targeted to the ubiquitin-dependent proteasome pathway by c-Cbl. Curr Biol. 2003;13:308-14 pubmed
    ..Subsequently, four vertebrate homologs were discovered; among these, the human homolog Sprouty 2 (hSpry2) contains the highest degree of sequence homology to the Drosophila protein...
  12. Medina G, Ehrlich L, Chen M, Khan M, Powell M, Carter C. Sprouty 2 binds ESCRT-II factor Eap20 and facilitates HIV-1 gag release. J Virol. 2011;85:7353-62 pubmed publisher
    ..Here we show (i) that VLP release requires the steady-state level of Sprouty 2 (Spry2) in COS-1 cells, (ii) that Spry2 binds the ESCRT-II component Eap20, (iii) that binding Eap20 permits Spry2 to ..
  13. Wong E, Lim J, Low B, Chen Q, Guy G. Evidence for direct interaction between Sprouty and Cbl. J Biol Chem. 2001;276:5866-75 pubmed
    ..This study was aimed at identifying proteins with which human SPRY2 (hSPRY2) interacts in an attempt to understand the mechanism by which Sprouty proteins exert their down-regulatory effects...
  14. de Alvaro C, Martinez N, Rojas J, Lorenzo M. Sprouty-2 overexpression in C2C12 cells confers myogenic differentiation properties in the presence of FGF2. Mol Biol Cell. 2005;16:4454-61 pubmed
    ..This work is the first evidence of the contribution of sprouty genes to myogenic differentiation in the presence of FGF2. ..
  15. Edwin F, Singh R, Endersby R, Baker S, Patel T. The tumor suppressor PTEN is necessary for human Sprouty 2-mediated inhibition of cell proliferation. J Biol Chem. 2006;281:4816-22 pubmed
    Sprouty family proteins are novel regulators of growth factor actions. Human Sprouty 2 (hSPRY2) inhibits the proliferation of a number of different cell types...
  16. Wong E, Fong C, Lim J, Yusoff P, Low B, Langdon W, et al. Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling. EMBO J. 2002;21:4796-808 pubmed
    ..is presented herein that describes the functional implications of the direct association between human Sprouty2 (hSpry2) and c-Cbl, and its impact on the cellular localization and signalling capacity of EGFR...
  17. Poppleton H, Edwin F, Jaggar L, Ray R, Johnson L, Patel T. Sprouty regulates cell migration by inhibiting the activation of Rac1 GTPase. Biochem Biophys Res Commun. 2004;323:98-103 pubmed
    ..The ability of TAT-hSPRY2 to inhibit migration was not altered by of RhoA(G14V) and cdc42(F28L)...
  18. Fritzsche S, Kenzelmann M, Hoffmann M, Muller M, Engers R, Grone H, et al. Concomitant down-regulation of SPRY1 and SPRY2 in prostate carcinoma. Endocr Relat Cancer. 2006;13:839-49 pubmed
    ..Indeed, down-regulation of SPRY1 and SPRY2 expression has been independently reported...
  19. Egan J, Hall A, Yatsula B, Bar Sagi D. The bimodal regulation of epidermal growth factor signaling by human Sprouty proteins. Proc Natl Acad Sci U S A. 2002;99:6041-6 pubmed
    ..Ectopically expressed full-length hSpry1 and hSpry2 induce the potentiation of EGFR-mediated mitogen-activated protein (MAP) kinase activation...
  20. Rubin C, Litvak V, Medvedovsky H, Zwang Y, Lev S, Yarden Y. Sprouty fine-tunes EGF signaling through interlinked positive and negative feedback loops. Curr Biol. 2003;13:297-307 pubmed
    ..When incorporated in signaling networks, the coupling of positive (Sprouty) to negative (Cbl) feedback loops can greatly enhance output diversification. ..
  21. 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
    ..Thus, these data highlight a novel negative and positive regulatory loop that allows for the controlled, homeostatic inhibition of RTK signaling. ..
  22. Yusoff P, Lao D, Ong S, Wong E, Lim J, Lo T, et al. Sprouty2 inhibits the Ras/MAP kinase pathway by inhibiting the activation of Raf. J Biol Chem. 2002;277:3195-201 pubmed
    ..b>hSpry2 was significantly more potent than mSpry1 or mSpry4 in inhibiting the Ras/MAP kinase pathway...
  23. Sanchez A, Setien F, Martinez N, Oliva J, Herranz M, Fraga M, et al. Epigenetic inactivation of the ERK inhibitor Spry2 in B-cell diffuse lymphomas. Oncogene. 2008;27:4969-72 pubmed publisher
    ..In this study we analysed whether epigenetic alterations of hSpry2 promoter occur in human lymphoid/hematopoietic malignancies...
  24. Fong C, Leong H, Wong E, Lim J, Yusoff P, Guy G. Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is crucial for its function. J Biol Chem. 2003;278:33456-64 pubmed
    ..Specifically, hSpry2 inhibits the fibroblast growth factor receptor (FGFR)-induced mitogen-activated protein kinase pathway but ..
  25. Ehrlich L, Medina G, Carter C. Sprouty2 regulates PI(4,5)P2/Ca2+ signaling and HIV-1 Gag release. J Mol Biol. 2011;410:716-25 pubmed publisher
    ..We show that Sprouty2 (Spry2), which binds PI(4,5)P(2) and PLC?, interfered with PI(4,5)P(2) in a manner similar to that of U73122, an ..
  26. 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...
  27. Martinez N, García Domínguez C, Domingo B, Oliva J, Zarich N, Sanchez A, et al. Sprouty2 binds Grb2 at two different proline-rich regions, and the mechanism of ERK inhibition is independent of this interaction. Cell Signal. 2007;19:2277-85 pubmed
    ..Most importantly, a double Sprouty2 mutant (hSpry2 P59AP304A), which is unable to bind Grb2, developed at a similar inhibition level of fibroblast growth factor ..
  28. Park T, Park J, Cheong H, Park B, Kim L, Heo J, et al. Genome-wide association study identifies ALLC polymorphisms correlated with FEV? change by corticosteroid. Clin Chim Acta. 2014;436:20-6 pubmed publisher
  29. Walker D, Land S. Regulation of vascular signalling by nuclear Sprouty2 in fetal lung epithelial cells: Implications for co-ordinated airway and vascular branching in lung development. Comp Biochem Physiol B Biochem Mol Biol. 2018;224:105-114 pubmed publisher
    Sprouty2 (Spry2) acts as a central regulator of tubular growth and branch patterning in the developing mammalian lung by controlling both magnitude and duration of growth factor signalling...
  30. Guo C, Degnin C, Laederich M, Lunstrum G, 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 pubmed publisher
    ..disturbance is mediated by the receptor's kinase activity and involves constitutive induction and activation of Spry2. Our findings suggest that activated Spry2 may interfere with c-Cbl-mediated ubiquitination of FGFR3 by ..
  31. Velasco A, Pallares J, Santacana M, Gatius S, Fernandez M, Domingo M, et al. Promoter hypermethylation and expression of sprouty 2 in endometrial carcinoma. Hum Pathol. 2011;42:185-93 pubmed publisher
    ..001). Sprouty 2 promoter methylation was detected in 31 (53.4%) of 58 endometrial carcinomas. Results from our study show that alterations in sprouty 2 may be involved in endometrial carcinogenesis by controlling cell proliferation. ..
  32. Chiu Y, Shan L, Huang H, Haupt C, Bessell C, Canaday D, et al. Sprouty-2 regulates HIV-specific T cell polyfunctionality. J Clin Invest. 2014;124:198-208 pubmed
    ..T cells that were stimulated with a high concentration of antigen upregulated sprouty-2 (SPRY2), a negative regulator of the MAPK/ERK pathway...
  33. Wang Y, Li Y, Fan X, Zhang Y, Wu J, Zhao Z. Early proliferation alteration and differential gene expression in human periodontal ligament cells subjected to cyclic tensile stress. Arch Oral Biol. 2011;56:177-86 pubmed publisher
    ..Seven up-regulated genes (PTGS2, KLF10, CDC42EP2, BHLHB2, SPRY2, IER3 and CCL2) were verified by quantitative RT-PCR, which supported the microarray results...
  34. Sun Q, Jackson R, Ng C, Guy G, Sivaraman J. Additional serine/threonine phosphorylation reduces binding affinity but preserves interface topography of substrate proteins to the c-Cbl TKB domain. PLoS ONE. 2010;5:e12819 pubmed publisher
    ..TKB domain and various substrate peptide motifs, including epidermal growth factor receptor (EGFR) and Sprouty2 (Spry2), and demonstrated that an intrapetidyl hydrogen bond forms between the (pY-1) arginine or (pY-2) asparagine and ..
  35. Kral R, Doriguzzi A, Mayer C, Krenbek D, Setinek U, Sutterlüty Fall H. Differential Effects of Variations at Codon 106 on Sprouty2 Functions in Lung Cancer-Derived Cells. J Cell Biochem. 2016;117:1822-32 pubmed publisher
    ..J. Cell. Biochem. 117: 1822-1832, 2016. © 2016 Wiley Periodicals, Inc. ..
  36. Feng Y, Wu C, Tsao C, Chang J, Lu P, Yeh K, et al. Deregulated expression of sprouty2 and microRNA-21 in human colon cancer: Correlation with the clinical stage of the disease. Cancer Biol Ther. 2011;11:111-21 pubmed
    ..Sprouty2 (Spry2) protein was shown to be downregulated in human cancers...
  37. Khan I, Yoo B, Masson O, Baron S, Corkery D, Dellaire G, et al. ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells. Oncogene. 2016;35:5759-5769 pubmed publisher
    ..This mechanism allows such cells to grow without adhesion to the ECM and is driven by ErbB2-induced activation of Mek, subsequent EGFR upregulation and further EGFR-dependent Perp loss. ..
  38. Zhao Y, Guo Y, Gu L, Fan X, Yang H, Chen Z, et al. Sensitized signalling between L-type Ca2+ channels and ryanodine receptors in the absence or inhibition of FKBP12.6 in cardiomyocytes. Cardiovasc Res. 2017;113:332-342 pubmed publisher
    ..Recent reports of high-resolution RyR structure show that the HD2 domain that binds to the SPRY2 domain of neighbouring subunit in FKBP-bound RyR1 is detached and invisible in FKBP-null RyR2...
  39. Schneider A, Cama G, Ghuman M, Hughes F, Gharibi B. Sprouty 2, an Early Response Gene Regulator of FosB and Mesenchymal Stem Cell Proliferation During Mechanical Loading and Osteogenic Differentiation. J Cell Biochem. 2017;118:2606-2614 pubmed publisher
    Sprouty 2 (Spry2), an inhibitor of MAP kinase signaling was previously shown by our group to be induced during mechanical loading of mesenchymal stem cells (MSCs)...
  40. Klimaschewski L, Sueiro B, Millan L. siRNA mediated down-regulation of Sprouty2/4 diminishes ischemic brain injury. Neurosci Lett. 2016;612:48-51 pubmed publisher
    ..A single injection of Sprouty2/4 siRNAs (25μM each) significantly decreased Spry2 and Spry4 mRNA levels two days later and diminished the size of the injury area in the subchronic phase following ..
  41. Haimov Kochman R, Ravhon A, Prus D, Greenfield C, Finci Yeheskel Z, S Goldman Wohl D, et al. Expression and regulation of Sprouty-2 in the granulosa-lutein cells of the corpus luteum. Mol Hum Reprod. 2005;11:537-42 pubmed
    ..The detection of Sprouty-2 mRNA and protein in human GLC may suggest a role for Sprouty-2 during the final stages of follicle maturation and CL formation. ..
  42. Shukla A, Rai K, Shukla V, Chaturvedi N, Bociek R, Pirruccello S, et al. Sprouty 2: a novel attenuator of B-cell receptor and MAPK-Erk signaling in CLL. Blood. 2016;127:2310-21 pubmed publisher
    ..We show that SPRY2 expression is significantly decreased in CLL cells, particularly from poor-prognosis patients compared with those ..
  43. Kousa Y, Roushangar R, Patel N, Walter A, Marangoni P, Krumlauf R, et al. IRF6 and SPRY4 Signaling Interact in Periderm Development. J Dent Res. 2017;96:1306-1313 pubmed publisher
    ..that encode receptor tyrosine kinase (RTK) signaling components, including members of the FGF pathway, EPHA3 and SPRY2, also contribute risk for isolated orofacial clefting...
  44. Lao D, Yusoff P, Chandramouli S, Philp R, Fong C, Jackson R, et al. 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. 2007;282:9117-26 pubmed
    In the context of fibroblast growth factor (FGF) signaling, Sprouty2 (Spry2) is the most profound inhibitor of the Ras/ERK pathway as compared with other Spry isoforms...
  45. Wu P, Yan J, Lai Y, Ng C, Li A, Jiang X, et al. Multiple regulatory modules are required for scale-to-feather conversion. Mol Biol Evol. 2017;: pubmed publisher
    ..feathers on scales (retinoic acid, ?-catenin), we identified novel scale-feather converters (Sox2, Zic1, Grem1, Spry2, Sox18) which induce one or more regulatory modules guiding these morphogenetic events...
  46. Zhao G, Bailey C, Feng Y, Rasko J, Lovicu F. Negative regulation of lens fiber cell differentiation by RTK antagonists Spry and Spred. Exp Eye Res. 2018;170:148-159 pubmed publisher
    ..in lens epithelial explants were transfected using different approaches to overexpress the different Spry (Spry1, Spry2) and Spred (Spred1, Spred2, Spred3) members, and we compared their ability to undergo FGF-induced fiber ..
  47. Dultz L, Dhar S, Ogilvie J, Heller K, Bar Sagi D, Patel K. Clinical and therapeutic implications of Sprouty2 feedback dysregulation in BRAF V600E-mutation-positive papillary thyroid cancer. Surgery. 2013;154:1239-44; discussion 1244-5 pubmed publisher
    ..Clinically, the behavior of BRAF+ PTC, however, varies from an indolent to an aggressive course. SPRY2 is a negative feedback regulator of the MAPK/ERK pathway...
  48. Hicks K, Patel T. Sprouty2 Protein Regulates Hypoxia-inducible Factor-? (HIF?) Protein Levels and Transcription of HIF?-responsive Genes. J Biol Chem. 2016;291:16787-801 pubmed publisher
    ..Sprouty2 (Spry2) is a modulator of receptor tyrosine kinase signaling and inhibits cell proliferation by a number of different ..
  49. Hwangpo T, Jordan J, Premsrirut P, Jayamaran G, Licht J, Iyengar R, et al. G Protein-regulated inducer of neurite outgrowth (GRIN) modulates Sprouty protein repression of mitogen-activated protein kinase (MAPK) activation by growth factor stimulation. J Biol Chem. 2012;287:13674-85 pubmed publisher
    ..Free Sprouty then in turn inhibits growth factor signaling. Thus, here we present a novel mechanism of how G(o/i)-coupled receptors can inhibit growth factor signaling to MAPK. ..
  50. Mayer C, Haigl B, Jantscher F, Siegwart G, Grusch M, Berger W, et al. Bimodal expression of Sprouty2 during the cell cycle is mediated by phase-specific Ras/MAPK and c-Cbl activities. Cell Mol Life Sci. 2010;67:3299-311 pubmed publisher
    ..Our results suggest that Sprouty2 abundance is the result of strictly coordinated activities of Ras and c-Cbl. ..
  51. Bassols J, Moreno Navarrete J, Carreras Badosa G, Diaz M, Prats Puig A, Palomer A, et al. Placental sprouty 2 (SPRY2): relation to placental growth and maternal metabolic status. Neonatology. 2014;106:120-5 pubmed publisher
    SPROUTY2 (SPRY2) is a membrane-associated protein expressed by placental macrophages with regulatory roles in tissue growth and development...
  52. Gao M, Patel R, Ahmad I, Fleming J, Edwards J, McCracken S, et al. SPRY2 loss enhances ErbB trafficking and PI3K/AKT signalling to drive human and mouse prostate carcinogenesis. EMBO Mol Med. 2012;4:776-90 pubmed publisher
    Loss of SPRY2 and activation of receptor tyrosine kinases are common events in prostate cancer (PC). However, the molecular basis of their interaction and clinical impact remains to be fully examined...
  53. Feng Y, Tsao C, Wu C, Chang J, Lu P, Yeh K, et al. Sprouty2 protein enhances the response to gefitinib through epidermal growth factor receptor in colon cancer cells. Cancer Sci. 2010;101:2033-8 pubmed publisher
    Sprouty2 (Spry2) is known to increase the expression of epidermal growth factor receptors (EGFR) by conjugating with c-Casitas B-lineage lymphoma (C-Cbl) to decrease protein degradation...
  54. Chiou Y, Liou S, Wong R, Chen C, Lee H. Nickel may contribute to EGFR mutation and synergistically promotes tumor invasion in EGFR-mutated lung cancer via nickel-induced microRNA-21 expression. Toxicol Lett. 2015;237:46-54 pubmed publisher
    ..Mechanistically, SPRY2 and RECK expressions were decreased by nickel-induced miR-21 via activation of the EGFR/NF-κB signaling pathway,..
  55. Natanson Yaron S, Anteby E, Greenfield C, Goldman Wohl D, Hamani Y, Hochner Celnikier D, et al. FGF 10 and Sprouty 2 modulate trophoblast invasion and branching morphogenesis. Mol Hum Reprod. 2007;13:511-9 pubmed
    ..siRNA of Spry2 was used to reduce its expression and to investigate the role of Sprouty 2 in villous explants outgrowths...
  56. Vieira A, Avila J, Daack Hirsch S, Dragan E, Felix T, Rahimov F, et al. Medical sequencing of candidate genes for nonsyndromic cleft lip and palate. PLoS Genet. 2005;1:e64 pubmed
    ..Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium ..
  57. Edwin F, Anderson K, Patel T. HECT domain-containing E3 ubiquitin ligase Nedd4 interacts with and ubiquitinates Sprouty2. J Biol Chem. 2010;285:255-64 pubmed publisher
    ..Herein, we demonstrate that Spry1 and Spry2, but not Spry3 or Spry4, associate with the HECT domain family E3 ubiquitin ligase, Nedd4...
  58. Milillo A, La Carpia F, Costanzi S, D Urbano V, Martini M, Lanuti P, et al. A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy. Eur J Hum Genet. 2015;23:1673-8 pubmed publisher
    ..From the bioinformatics analysis a p.(Arg119Trp) variant in the SPRY2 gene was identified as the probable disease-causing mutation...
  59. Glienke J, Fenten G, Seemann M, Sturz A, Thierauch K. Human SPRY2 inhibits FGF2 signalling by a secreted factor. Mech Dev. 2000;96:91-9 pubmed
    ..Here we describe the role of SPRY2, a human homologue of Spry, in human FGF2 signalling...
  60. Lim J, Wong E, Ong S, Yusoff P, Low B, Guy G. Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain. J Biol Chem. 2000;275:32837-45 pubmed
    ..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...
  61. Patel R, Gao M, Ahmad I, Fleming J, Singh L, Rai T, et al. Sprouty2, PTEN, and PP2A interact to regulate prostate cancer progression. J Clin Invest. 2013;123:1157-75 pubmed publisher
    ..The negative regulators of these pathways, including sprouty2 (SPRY2), protein phosphatase 2A (PP2A), and phosphatase and tensin homolog (PTEN), are commonly inactivated in prostate ..
  62. Zhang W, Du Z, Zhu J, Yu J, Xu Y. Sprouty2 suppresses the inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes through regulating the Raf/ERK and PTEN/AKT signals. Mol Immunol. 2015;67:532-9 pubmed publisher
    ..Sprouty2 (SPRY2) has been known as a tumor suppressor by preventing both ERK and AKT signaling activations...
  63. Ma Y, Yu S, Zhao W, Lu Z, Chen J. miR-27a regulates the growth, colony formation and migration of pancreatic cancer cells by targeting Sprouty2. Cancer Lett. 2010;298:150-8 pubmed publisher
    ..By using a reporter-screening assay, we discovered that the 3'UTR of Sprouty2 (Spry2) carried a putative miR-27a binding site...
  64. Rathmanner N, Haigl B, Vanas V, Doriguzzi A, Gsur A, Sutterlüty Fall H. Sprouty2 but not Sprouty4 is a potent inhibitor of cell proliferation and migration of osteosarcoma cells. FEBS Lett. 2013;587:2597-605 pubmed publisher
    ..Sequences within the NH2-terminus are responsible for the specific inhibitory function of Sprouty2 protein. ..
  65. Barbáchano A, Fernández Barral A, Pereira F, Segura M, Ordóñez Morán P, Carrillo de Santa Pau E, et al. SPROUTY-2 represses the epithelial phenotype of colon carcinoma cells via upregulation of ZEB1 mediated by ETS1 and miR-200/miR-150. Oncogene. 2016;35:2991-3003 pubmed publisher
    SPROUTY-2 (SPRY2) is a modulator of tyrosine kinase receptor signaling with receptor- and cell type-dependent inhibitory or enhancing effects. Studies on the action of SPRY2 in major cancers are conflicting and its role remains unclear...
  66. Acunzo M, Romano G, Palmieri D, Laganà A, Garofalo M, Balatti V, et al. Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2. Proc Natl Acad Sci U S A. 2013;110:8573-8 pubmed publisher
    ..In addition, we identify both direct and indirect mechanisms by which miR-27a can regulate both MET and EGFR. Thus, we propose a mechanism for MET and EGFR axis regulation that may lead to the development of therapeutics in lung cancer. ..
  67. Gao X, Hicks K, Neumann P, Patel T. Hypoxia inducible factors regulate the transcription of the sprouty2 gene and expression of the sprouty2 protein. PLoS ONE. 2017;12:e0171616 pubmed publisher
    Receptor Tyrosine Kinase (RTK) signaling plays a major role in tumorigenesis and normal development. Sprouty2 (Spry2) attenuates RTK signaling and inhibits processes such as angiogenesis, cell proliferation, migration and survival, which ..
  68. Jagomagi T, Nikopensius T, Krjutskov K, Tammekivi V, Viltrop T, Saag M, et al. MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate. Eur J Oral Sci. 2010;118:213-20 pubmed publisher
    ..This study provides further evidence implicating MSX1 and MTHFR in the etiology of nonsyndromic CL/P across different populations...
  69. Miraoui H, Ringe J, Häupl T, Marie P. Increased EFG- and PDGFalpha-receptor signaling by mutant FGF-receptor 2 contributes to osteoblast dysfunction in Apert craniosynostosis. Hum Mol Genet. 2010;19:1678-89 pubmed publisher
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    ..Parallel paradigms for non-ESCRT roles in virus budding and cytokinesis will be discussed. ..
  71. Grassian A, Schafer Z, Brugge J. ErbB2 stabilizes epidermal growth factor receptor (EGFR) expression via Erk and Sprouty2 in extracellular matrix-detached cells. J Biol Chem. 2011;286:79-90 pubmed publisher
    ..These results provide further insight into the ErbB2-driven anchorage independence of tumor cells and provide a new mechanism for regulation of EGFR and ?1 integrin expression in ECM-detached cells. ..
  72. Holgren C, Dougherty U, Edwin F, Cerasi D, Taylor I, Fichera A, et al. Sprouty-2 controls c-Met expression and metastatic potential of colon cancer cells: sprouty/c-Met upregulation in human colonic adenocarcinomas. Oncogene. 2010;29:5241-53 pubmed publisher
    ..Thus, in colon cancer sprouty functions as an oncogene and its effects are mediated in part by c-Met upregulation. ..
  73. Masoumi Moghaddam S, Amini A, Wei A, Robertson G, Morris D. Sprouty 2 protein, but not Sprouty 4, is an independent prognostic biomarker for human epithelial ovarian cancer. Int J Cancer. 2015;137:560-70 pubmed publisher
    ..In the present study, the expression status of Spry2 and Spry4 proteins and its clinical relevance in human epithelial ovarian cancer (EOC) were investigated ..
  74. Mu Z, Wang H, Zhang J, Li Q, Wang L, Guo X. KAI1/CD82 suppresses hepatocyte growth factor-induced migration of hepatoma cells via upregulation of Sprouty2. Sci China C Life Sci. 2008;51:648-54 pubmed publisher
    ..It is demonstrated that KAI1/CD82 suppresses HGF-induced migration of hepatoma cells via upregulation of Sprouty2. ..