Gene Symbol: Frs3
Description: fibroblast growth factor receptor substrate 3
Alias: 4930417B13Rik, AI449674, Frs2beta, Snt2, fibroblast growth factor receptor substrate 3, FGFR substrate 3, FRS2-beta, suc1-associated neurotrophic factor target 2 (FGFR signalling adaptor)
Species: mouse
Products:     Frs3

Top Publications

  1. Hoch R, Soriano P. Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development. Development. 2006;133:663-73 pubmed
    ..Biochemical studies have implicated Fgf receptor-specific substrates (Frs2, Frs3) as the principal mediators of Fgfr1 signal transduction to the MAPK and PI3K pathways...
  2. McDougall K, Kubu C, Verdi J, Meakin S. Developmental expression patterns of the signaling adapters FRS-2 and FRS-3 during early embryogenesis. Mech Dev. 2001;103:145-8 pubmed
    Two fibroblast growth factor (FGF) receptor substrates (FRS2 and FRS3) are involved in downstream signaling from activated FGF receptors and neurotrophin-activated Trk receptors...
  3. Ranzi V, Meakin S, Miranda C, Mondellini P, Pierotti M, Greco A. The signaling adapters fibroblast growth factor receptor substrate 2 and 3 are activated by the thyroid TRK oncoproteins. Endocrinology. 2003;144:922-8 pubmed
    ..In this paper, we investigate the role of FRS2 and FRS3, two related adapter proteins activated by fibroblast growth factor and NTRK1 receptors, in the signaling of the ..
  4. Gotoh N, Ito M, Yamamoto S, Yoshino I, Song N, Wang Y, et al. Tyrosine phosphorylation sites on FRS2alpha responsible for Shp2 recruitment are critical for induction of lens and retina. Proc Natl Acad Sci U S A. 2004;101:17144-9 pubmed
    ..These experiments demonstrate that intracellular signals that depend on specific tyrosine residues in FRS2alpha lie upstream of gene products critical for induction of lens and retina. ..
  5. Hryciw T, MacDonald J, Phillips R, Seah C, Pasternak S, Meakin S. The fibroblast growth factor receptor substrate 3 adapter is a developmentally regulated microtubule-associated protein expressed in migrating and differentiated neurons. J Neurochem. 2010;112:924-39 pubmed publisher
    ..signal primarily through the FGF receptor substrate (Frs) adapters, which include Frs2/Frs2alpha and Frs3/Frs2beta. While some studies suggest that Frs3 can compensate for the loss of Frs2 in transfected cells, the lack of an ..
  6. Zhang Y, McKeehan K, Lin Y, Zhang J, Wang F. Fibroblast growth factor receptor 1 (FGFR1) tyrosine phosphorylation regulates binding of FGFR substrate 2alpha (FRS2alpha) but not FRS2 to the receptor. Mol Endocrinol. 2008;22:167-75 pubmed
    ..The FGFR substrate 2 (FRS2) family consists of two members, FRS2alpha and FRS2beta, and has been shown to recruit multiple signaling molecules, including Grb2 and Shp2, to FGFR1...
  7. 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;583:807-14 pubmed publisher
    ..protein family comprises FRS2alpha, a well-known central mediator for fibroblast growth factor signaling, and FRS2beta, whose endogenous expression pattern and function are not yet defined...
  8. Ono K, Kita T, Sato S, O Neill P, Mak S, Paschaki M, et al. FGFR1-Frs2/3 signalling maintains sensory progenitors during inner ear hair cell formation. PLoS Genet. 2014;10:e1004118 pubmed publisher
    ..We suggest that FGF signaling, through the activation of MAP kinase, is necessary for the maintenance of sensory progenitors and commits precursors to sensory cell differentiation in the mammalian cochlea. ..
  9. Ong S, Guy G, Hadari Y, Laks S, Gotoh N, Schlessinger J, et al. FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors. Mol Cell Biol. 2000;20:979-89 pubmed
    ..The two members of the FRS2 family, FRS2alpha and FRS2beta, are structurally very similar...

More Information


  1. Zhou L, McDougall K, Kubu C, Verdi J, Meakin S. Genomic organization and comparative sequence analysis of the mouse and human FRS2, FRS3 genes. Mol Biol Rep. 2003;30:15-25 pubmed
    The signaling adapter proteins FRS2 and FRS3 are implicated in the transmission of extracellular signals from nerve growth factor (NGF) or fibroblast growth factor (FGF) receptors to the Ras/mitogen-activated protein kinase signaling ..
  2. 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;564:14-8 pubmed
    FRS2alpha and FRS2beta, two members of the FRS2 family of docking proteins, become tyrosine phosphorylated in response to fibroblast growth factor (FGF) or nerve growth factor (NGF) stimulation...
  3. Nandi S, Gutin G, Blackwood C, Kamatkar N, Lee K, Fishell G, et al. FGF-Dependent, Context-Driven Role for FRS Adapters in the Early Telencephalon. J Neurosci. 2017;37:5690-5698 pubmed publisher
    ..Here, we used the developing mouse telencephalon as an example to study the role of the FRS adapters FRS2 and FRS3 in mediating the functions of FGFRs...
  4. Avery A, Figueroa C, Vojtek A. UNC-51-like kinase regulation of fibroblast growth factor receptor substrate 2/3. Cell Signal. 2007;19:177-84 pubmed
    ..We demonstrate that siRNA targeting ULK2 in mouse P19 cells results in elevated FGFR1 mediated FRS3 and SHP2 tyrosyl phosphorylation...
  5. Chikamori M, Fujimoto J, Tokai Nishizumi N, Yamamoto T. Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and their involvement in cell transformation. Oncogene. 2007;26:2950-4 pubmed
    ..This raises a possibility that SNT family proteins play significant roles in cellular transformation triggered by NPM-ALK, which though remains to be verified. ..
  6. Brewer J, Molotkov A, Mazot P, Hoch R, Soriano P. Fgfr1 regulates development through the combinatorial use of signaling proteins. Genes Dev. 2015;29:1863-74 pubmed publisher
    ..This suggests that Erk1/2-independent signaling pathways are functionally important for Fgf signaling in vivo. ..