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Shp2, an SH2-containing Protein-tyrosine Phosphatase, Positively Regulates Receptor Tyrosine Kinase Signaling by Dephosphorylating and Inactivating the Inhibitor Sprouty
Open accessAbstract
Src homology 2-containing phosphotyrosine phosphatase (Shp2) functions as a positive effector in receptor tyrosine kinase (RTK) signaling immediately proximal to activated receptors. However, neither its physiological substrate(s) nor its mechanism of action in RTK signaling has been defined. In this study, we demonstrate that Sprouty (Spry) is a possible target of Shp2. Spry acts as a conserved inhibitor of RTK signaling, and tyrosine phosphorylation of Spry is indispensable for its inhibitory activity. Shp2 was able to dephosphorylate fibroblast growth factor receptor-induced phosphotyrosines on Spry both in vivo and in vitro. Shp2-mediated dephosphorylation of Spry resulted in dissociation of Spry from Grb2. Furthermore, Shp2 could reverse the inhibitory effect of Spry on FGF-induced neurite outgrowth and MAP kinase activation. These findings suggest that Shp2 acts as a positive regulator in RTK signaling by dephosphorylating and inactivating Spry.
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Cites
Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras.
Bennett, A. M., Tang, T. L., Sugimoto, S., Walsh, C. T., & Neel, B. G. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.15.7335 · Cited by 397
Cited by
Hyperactive Ras in developmental disorders and cancer
Schubbert, S., Shannon, K., & Bollag, G. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2109 · Cited by 1,583
Integrating signals from RTKs to ERK/MAPK
McKay, M. M., & Morrison, D. K. (2007) · Oncogene · doi:10.1038/sj.onc.1210394 · Cited by 621
Raf Family Kinases: Old Dogs Have Learned New Tricks
Matallanas, D., Birtwistle, M., Romano, D., Zebisch, A., Rauch, J., von Kriegsheim, A., & Kolch, W. (2011) · Genes & Cancer · doi:10.1177/1947601911407323 · Cited by 386
The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway
Dance, M., Montagner, A., Salles, J.-P., Yart, A., & Raynal, P. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2007.10.002 · Cited by 361
NOONAN SYNDROME AND RELATED DISORDERS: Genetics and Pathogenesis
Tartaglia, M., & Gelb, B. D. (2005) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.6.080604.162305 · Cited by 355
Metadata
- Authors
- Hanafusa, H., Torii, S., Yasunaga, T., Matsumoto, K., & Nishida, E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 279
- Issue
- 22
- Pages
- 22992-22995
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2077471676
- Cited by
- 174
- References
- 1
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Shp2, an SH2-containing Protein-tyrosine Phosphatase, Positively Regulates Receptor Tyrosine Kinase Signaling by Dephosphorylating and Inactivating the Inhibitor Sprouty. https://app.cochat.ai/papers/10.1074/jbc.m312498200
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- Hanafusa, H., Torii, S., Yasunaga, T., Matsumoto, K., & Nishida, E. (2004). Shp2, an SH2-containing Protein-tyrosine Phosphatase, Positively Regulates Receptor Tyrosine Kinase Signaling by Dephosphorylating and Inactivating the Inhibitor Sprouty. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m312498200
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