Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

FRS2

  • Noriko Gotoh
Reference work entry
First Online:
DOI: https://doi.org/10.1007/978-3-319-67199-4_356
How to cite

Synonyms

 FRS2 family members: FRS2α;  FRS2ß;  FRS3;  suc 1-associated neurotrophic factor target (SNT-1);  suc 1-associated neurotrophic factor target (SNT-2)

Historical Background

FRS2 stands for fibroblast growth factor (FGF) receptor substrate 2. The FGF receptor substrate 1 is phospholipase (PLC) γ, which was identified as the first substrate of FGF receptor tyrosine kinases (Gotoh et al. 2004). Historically, SNT was identified as a protein that is tyrosine phosphorylated in response to nerve growth factor (NGF) or  FGF in PC12 cells and can bind to p13suc1, a yeast cyclin–dependent kinase binding protein, immobilized on agarose (Rabin et al. 1993). It was reported that there is a good correlation between the tyrosine phosphorylation of SNT and differentiation of PC12 cells. Then FRS2 was purified and cloned as a novel protein that is tyrosine phosphorylated in NIH3T3 cells in response to FGF (Kouhara et al. 1997). It turned out to be the same protein as SNT. Another protein that...

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References

  1. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16(2):139–49.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Gotoh N. Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins. Cancer Sci. 2008;99(7):1319–25.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Gotoh N, Tsuchida N. Membrane-lined docking protein. In: Encyclopedia of cancer. 2nd ed. Heiderlberg: Springer; 2008. p. 1819–23.Google Scholar
  4. Gotoh N, Laks S, Nakashima M, Lax I, Schlessinger J. FRS2 family docking proteins with overlapping roles in activation of MAP kinase have distinct spatial-temporal patterns of expression of their transcripts. FEBS Lett. 2004;564(1–2):14–8.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Gotoh N, Manova K, Tanaka S, Murohashi M, Hadari Y, Lee A, et al. The docking protein FRS2{alpha} is an essential component of multiple fibroblast growth factor responses during early mouse development. Mol Cell Biol. 2005;25(10):4105–16.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Iejima D, Minegishi Y, Takenaka K, Siswanto A, Watanabe M, Huang L, et al. FRS2beta, a potential prognostic gene for non-small cell lung cancer, encodes a feedback inhibitor of EGF receptor family members by ERK binding. Oncogene. 2010;29(21):3087–99.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar-Sagi D, Lax I, et al. A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway. Cell. 1997;89(5):693–702.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117–34.PubMedPubMedCentralCrossRefGoogle Scholar
  9. McDougall K, Kubu C, Verdi JM, Meakin SO. Developmental expression patterns of the signaling adapters FRS-2 and FRS-3 during early embryogenesis. Mech Dev. 2001;103(1–2):145–8.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Minegishi Y, Iwanari H, Mochizuki Y, Horii T, Hoshino T, Kodama T, et al. Prominent expression of FRS2beta protein in neural cells and its association with intracellular vesicles. FEBS Lett. 2009;583(4):807–14.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Murohashi M, Nakamura T, Tanaka S, Ichise T, Yoshida N, Yamamoto T, et al. An FGF4-FRS2alpha-Cdx2 axis in trophoblast stem cells induces Bmp4 to regulate proper growth of early mouse embryos. Stem Cells. 2010;28(1):113–21.PubMedPubMedCentralGoogle Scholar
  12. Pawson T. Dynamic control of signaling by modular adaptor proteins. Curr Opin Cell Biol. 2007;19(2):112–6.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Rabin SJ, Cleghon V, Kaplan DR. SNT, a differentiation-specific target of neurotrophic factor-induced tyrosine kinase activity in neurons and PC12 cells. Mol Cell Biol. 1993;13(4):2203–13.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Sato T, Gotoh N. The FRS2 family of docking/scaffolding adaptor proteins as therapeutic targets of cancer treatment. Expert Opin Ther Targets. 2009;13(6):689–700.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Sato T, Shimazaki T, Naka H, Fukami S, Satoh Y, Okano H, et al. FRS2alpha regulates Erk levels to control a self-renewal target Hes1 and proliferation of FGF-responsive neural stem/progenitor cells. Stem Cells. 2010;28(9):1661–73.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Xu H, Lee KW, Goldfarb M. Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins. J Biol Chem. 1998;273(29):17987–90.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Zhang Y, Zhang J, Lin Y, Lan Y, Lin C, Xuan JW, et al. Role of epithelial cell fibroblast growth factor receptor substrate 2alpha in prostate development, regeneration and tumorigenesis. Development. 2008;135(4):775–84.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institute of Medical ScienceThe University of Tokyo, Minato-kuTokyoJapan