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Sprouty, an Intracellular Inhibitor of Ras Signaling
Open accessAbstract
Sprouty was identified in a genetic screen as an inhibitor of Drosophila EGF receptor signaling. The Egfr triggers cell recruitment in the eye, and sprouty- eyes have excess photoreceptors, cone cells, and pigment cells. Sprouty's function is, however, more widespread. We show that it also interacts genetically with the receptor tyrosine kinases Torso and Sevenless, and it was first discovered through its effect on FGF receptor signaling. In contrast to an earlier proposal that Sprouty is extracellular, we show by biochemical analysis that Sprouty is an intracellular protein, associated with the inner surface of the plasma membrane. Sprouty binds to two intracellular components of the Ras pathway, Drk and Gap1. Our results indicate that Sprouty is a widespread inhibitor of Ras pathway signal transduction.
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“Four of the validated miR-21 target genes are known negative regulators of the Ras/MEK/ERK pathway: sprouty 1 (Spry1), sprouty 2 (Spry2), B-cell translocation gene 2 (Btg2), and programmed cell death 4 (Pdcd4).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Casci et al., 1999
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Cites
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Thum, T., Gross, C., Fiedler, J., Fischer, T., Kissler, S., Bussen, M., Galuppo, P., Just, S., Rottbauer, W., Frantz, S., et al. (2008) · Nature · doi:10.1038/nature07511 · Cited by 2,349
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Metadata
- Authors
- Casci, T., Vinós, J., & Freeman, M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Freeman, Matthew
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-03
- Volume
- 96
- Issue
- 5
- Pages
- 655-665
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2082773871
- Cited by
- 467
- References
- 62
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 13 · 2020: 13 · 2019: 4 · 2018: 10 · 2017: 11 · 2016: 19 · 2015: 16 · 2014: 12 · 2013: 15 · 2012: 17
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- Sprouty, Ras signaling, EGF receptor signaling, Drosophila, Torso receptor, FGF receptor signaling, DRK, GAP1, receptor tyrosine kinase, pigment cells, plasma membrane
- MeSH terms
- Animals, Cells, Cultured, Cysteine, Depression, Chemical, Drosophila melanogaster, Eye, Eye Abnormalities, Eye Proteins, Membrane Glycoproteins, Membrane Proteins, Morphogenesis, Proteins, Signal Transduction, ras Proteins, Insect Proteins, ras GTPase-Activating Proteins, Receptor Protein-Tyrosine Kinases, Drosophila Proteins, Macromolecular Substances, ErbB Receptors
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