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JOURNAL ARTICLES
Sprouty is a general inhibitor of receptor tyrosine kinase signaling
A. Reich, A. Sapir, B. Shilo
Development 1999 126: 4139-4147;
A. Reich
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A. Sapir
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B. Shilo
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Summary

Sprouty was originally identified as an inhibitor of Drosophila FGF receptor signaling during tracheal development. By following the capacity of ectopic Sprouty to abolish the pattern of activated MAP kinase in embryos, we show that Sprouty can inhibit other receptor tyrosine kinase (RTK) signaling pathways, namely the Heartless FGF receptor and the EGF receptor. Similarly, in wing imaginal discs, ectopic Sprouty abolishes activated MAP kinase induced by the EGF receptor pathway. Sprouty expression is induced by the EGFR pathway in some, but not all, tissues in which EGFR is activated, most notably in follicle cells of the ovary, the wing imaginal disc and the eye disc. In the ovary, induction of sprouty expression follows the pattern of EGFR activation in the follicle cells. Generation of homozygous sprouty mutant follicle-cell clones demonstrates an essential role for Sprouty in restricting EGFR activation throughout oogenesis. At the stage when dorso-ventral polarity of the follicle cells is established, Sprouty limits the ventral expansion of the activating Gurken signal. Later, when dorsal appendage fates are determined, reduction of signaling by Sprouty facilitates the induction of inter-appendage cell fates. The capacity of Sprouty to reduce or eliminate accumulation of activated MAP kinase indicates that in vivo it intersects with the pathway upstream to MAP kinase. The ability of ectopic Sprouty to rescue lethality caused by activated Raf suggests that it may impinge upon the pathway by interacting with Raf or downstream to it.

Reference

    1. Bergmann A.,
    2. Agapite J.,
    3. McCall K.,
    4. Steller H.
    (1998) The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling. Cell 95, 331–341
    OpenUrlCrossRefPubMedWeb of Science
    1. Brand A. H.,
    2. Perrimon N.
    (1994) Raf acts downstream of the EGF receptor to determine dorsoventral polarity during Drosophila oogenesis. Genes Dev 8, 629–639
    OpenUrlAbstract/FREE Full Text
    1. Casci T.,
    2. Vinos J.,
    3. Freeman M.
    (1999) Sprouty, an Intracellular Inhibitor of Ras Signaling. Cell 96, 655–665
    OpenUrlCrossRefPubMedWeb of Science
    1. Cavallo R. A.,
    2. Cox R. T.,
    3. Moline M. M.,
    4. Roose J.,
    5. Polevoy G. A.,
    6. Clevers H.,
    7. Peifer M.,
    8. Bejsovec A.
    (1998) Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 395, 604–608
    OpenUrlCrossRefPubMed
    1. Chen Y.,
    2. Struhl G.
    (1996) Dual roles for patched in sequestering and transducing Hedgehog. Cell 87, 553–563
    OpenUrlCrossRefPubMedWeb of Science
    1. de Maximy A. A.,
    2. Nakatake Y.,
    3. Moncada S.,
    4. Itoh N.,
    5. Thiery J. P.,
    6. Bellusci S.
    (1999) Cloning and expression pattern of a mouse homologue of Drosophila sprouty in the mouse embryo. Mech. Dev 81, 213–216
    OpenUrlCrossRefPubMedWeb of Science
    1. Duffy J. B.,
    2. Harrison D. A.,
    3. Perrimon N.
    (1998) Identifying loci required for follicular patterning using directed mosaics. Development 125, 2263–2271
    OpenUrlAbstract
    1. Freeman M.,
    2. Klambt C.,
    3. Goodman C. S.,
    4. Rubin G. M.
    (1992) The argos gene encodes a diffusible factor that regulates cell fate decisions in the Drosophila eye. Cell 69, 963–975
    OpenUrlCrossRefPubMedWeb of Science
    1. Gabay L.,
    2. Seger R.,
    3. Shilo B. Z.
    (1997) In situ activation pattern of Drosophila EGF receptor pathway during development. Science 277, 1103–1106
    OpenUrlAbstract/FREE Full Text
    1. Gabay L.,
    2. Seger R.,
    3. Shilo B. Z.
    (1997) MAP kinase in situ activation atlas during Drosophila embryogenesis. Development 124, 3535–3541
    OpenUrlAbstract
    1. Ghiglione C.,
    2. Carraway K. L. I.,
    3. Amundadottir L. T.,
    4. Boswell R. E.,
    5. Perrimon N.,
    6. Duffy J. B.
    (1999) The transmembrane molecule Kekkon 1 acts in a feedback loop to negatively regulate the activity of the Drosophila EGF receptor during oogenesis. Cell 96, 847–856
    OpenUrlCrossRefPubMedWeb of Science
    1. Golembo M.,
    2. Schweitzer R.,
    3. Freeman M.,
    4. Shilo B. Z.
    (1996) Argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop. Development 122, 223–230
    OpenUrlAbstract
    1. Hacohen N.,
    2. Kramer S.,
    3. Sutherland D.,
    4. Hiromi Y.,
    5. Krasnow M. A.
    (1998) sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell 92, 253–263
    OpenUrlCrossRefPubMedWeb of Science
    1. Hemmati-Brivanlou A.,
    2. Kelly O. G.,
    3. Melton D. A.
    (1994) Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity. Cell 77, 283–295
    OpenUrlCrossRefPubMedWeb of Science
    1. Kramer S.,
    2. Okabe M.,
    3. Hacohen N.,
    4. Krasnow M. A.,
    5. Hiromi Y.
    (1999) Sprouty: a common antagonist of FGF and EGF signaling pathways in Drosophila. Development 126, 2515–2525
    OpenUrlAbstract
    1. Lai Z. C.,
    2. Rubin G. M.
    (1992) Negative control of photoreceptor development in Drosophila by the product of the yan gene, an ETS domain protein. Cell 70, 609–620
    OpenUrlCrossRefPubMedWeb of Science
    1. Martin-Blanco E.,
    2. Gampel A.,
    3. Ring J.,
    4. Virdee K.,
    5. Kirov N.,
    6. Tolkovsky A. M.,
    7. Martinez-Arias A.
    (1998) puckered encodes a phosphatase that mediates a feedback loop regulating JNK activity during dorsal closure in Drosophila. Genes Dev 12, 557–570
    OpenUrlAbstract/FREE Full Text
    1. Musacchio M.,
    2. Perrimon N.
    (1996) The Drosophila kekkon genes: novel members of both the leucine-rich repeat and immunoglobulin superfamilies expressed in the CNS. Dev. Biol 178, 63–76
    OpenUrlCrossRefPubMedWeb of Science
    1. Nakao A.,
    2. Afrakhte M.,
    3. Moren A.,
    4. Nakayama T.,
    5. Christian J. L.,
    6. Heuchel R.,
    7. Itoh S.,
    8. Kawabata M.,
    9. Heldin N. E.,
    10. Heldin C. H.,
    11. ten Dijke P.
    (1997) Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 389, 631–635
    OpenUrlCrossRefPubMed
    1. Neumann C. J.,
    2. Cohen S. M.
    (1998) Boundary Formation in Drosophila Wing: Notch Activity Attenuated by the POU Protein Nubbin. Science 281, 409–413
    OpenUrlAbstract/FREE Full Text
    1. Noguchi T.,
    2. Metz R.,
    3. Chen L.,
    4. Mattei M. G.,
    5. Carrasco D.,
    6. Bravo R.
    (1993) Structure, mapping, and expression of erp, a growth factor-inducible gene encoding a nontransmembrane protein tyrosine phosphatase, and effect of ERP on cell growth. Mol. Cell. Biol 13, 5195–5205
    OpenUrlAbstract/FREE Full Text
    1. Paroush Z.,
    2. Wainwright S. M.,
    3. Ish-Horowicz D.
    (1997) Torso signalling regulates terminal patterning in Drosophila by antagonising Groucho-mediated repression. Development 124, 3827–3834
    OpenUrlAbstract
    1. Peri F.,
    2. Bokel C.,
    3. Roth S.
    (1999) Local gurken signaling and dynamic MAPK activation during Drosophila oogenesis. Mech. Dev 81, 75–88
    OpenUrlCrossRefPubMedWeb of Science
    1. Queenan A. M.,
    2. Ghabrial A.,
    3. Schupbach T.
    (1997) Ectopic activation of torpedo/Egfr, a Drosophila receptor tyrosine kinase, dorsalizes both the eggshell and the embryo. Development 124, 3871–3880
    OpenUrlAbstract
    1. Ray R. P.,
    2. Schupbach T.
    (1996) Intercellular signaling and the polarization of body axes during Drosophila oogenesis. Genes Dev 10, 1711–1723
    OpenUrlFREE Full Text
    1. Roth S.,
    2. Schupbach T.
    (1994) The relationship between ovarian and embryonic dorsoventral patterning in Drosophila. Development 120, 2245–2257
    OpenUrlAbstract
    1. Sapir A.,
    2. Schweitzer R.,
    3. Shilo B. Z.
    (1998) Sequential activation of theEGF receptor pathway during Drosophila oogenesis establishes the dorsoventral axis. Development 125, 191–200
    OpenUrlAbstract
    1. Sasai Y.,
    2. Lu B.,
    3. Steinbeisser H.,
    4. De Robertis E. M.
    (1995) Regulation of neural induction by the Chd and Bmp-4 antagonistic patterning signals in Xenopus. Nature 376, 333–336
    OpenUrlCrossRefPubMed
    1. Sawamoto K.,
    2. Okano H.,
    3. Kobayakawa Y.,
    4. Hayashi S.,
    5. Mikoshiba K.,
    6. Tanimura T.
    (1994) The function of argos in regulating cell fate decisions during Drosophila eye and wing vein development. Dev. Biol 164, 267–276
    OpenUrlCrossRefPubMedWeb of Science
    1. Schupbach T.
    (1987) Germ line and soma cooperate during oogenesis to establish the dorsoventral pattern of egg shell and embryo in Drosophila melanogaster. Cell 49, 699–707
    OpenUrlCrossRefPubMedWeb of Science
    1. Schweitzer R.,
    2. Howes R.,
    3. Smith R.,
    4. Shilo B. Z.,
    5. Freeman M.
    (1995) Inhibition of Drosophila EGF receptor activation by the secreted protein Argos. Nature 376, 699–702
    OpenUrlCrossRefPubMed
    1. Schweitzer R.,
    2. Shaharabany M.,
    3. Seger R.,
    4. Shilo B. Z.
    (1995) Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. Genes Dev 9, 1518–1529
    OpenUrlAbstract/FREE Full Text
    1. Sturtevant M. A.,
    2. Roark M.,
    3. Bier E.
    (1993) The Drosophila rhomboid gene mediates the localized formation of wing veins and interacts genetically with components of the EGF-R signaling pathway. Genes Dev 7, 961–973
    OpenUrlAbstract/FREE Full Text
    1. Tefft J. D.,
    2. Lee M.,
    3. Smith S.,
    4. Leinwand M.,
    5. Zhao J.,
    6. Bringas P. Jr.,
    7. Crowe D. L.,
    8. Warburton D.
    (1999) Conserved function of mSpry-2, a murine homolog of Drosophila sprouty, which negatively modulates respiratory organogenesis. Curr. Biol 9, 219–222
    OpenUrlCrossRefPubMedWeb of Science
    1. Therrien M.,
    2. Michaud N. R.,
    3. Rubin G. M.,
    4. Morrison D. K.
    (1996) KSR modulates signal propagation within the MAPK cascade. Genes Dev 10, 2684–2695
    OpenUrlAbstract/FREE Full Text
    1. Therrien M.,
    2. Wong A. M.,
    3. Rubin G. M.
    (1998) CNK, a RAF-binding multidomain protein required for RAS signaling. Cell 95, 343–353
    OpenUrlCrossRefPubMedWeb of Science
    1. Tsuneizumi K.,
    2. Nakayama T.,
    3. Kamoshida Y.,
    4. Kornberg T. B.,
    5. Christian J. L.,
    6. Tabata T.
    (1997) Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature 389, 627–631
    OpenUrlCrossRefPubMed
    1. Wasserman J. D.,
    2. Freeman M.
    (1998) An autoregulatory cascade of EGF receptor signaling patterns the Drosophila egg. Cell 95, 355–364
    OpenUrlCrossRefPubMedWeb of Science
    1. Zimmerman L. B.,
    2. De Jesus-Escobar J. M.,
    3. Harland R. M.
    (1996) The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Cell 86, 599–606
    OpenUrlCrossRefPubMedWeb of Science
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JOURNAL ARTICLES
Sprouty is a general inhibitor of receptor tyrosine kinase signaling
A. Reich, A. Sapir, B. Shilo
Development 1999 126: 4139-4147;
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JOURNAL ARTICLES
Sprouty is a general inhibitor of receptor tyrosine kinase signaling
A. Reich, A. Sapir, B. Shilo
Development 1999 126: 4139-4147;

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