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Gene Review:

Frs2 - fibroblast growth factor receptor substrate 2

Mus musculus

Synonyms: 4732458E18, C330018A15Rik, FGFR substrate 2, FGFR-signaling adaptor SNT, FRS2-alpha, ...

Zhang, Y. et al., Hoch, R.V. et al., Kontaridis, M.I. et al., Liu, Z. et al., Gotoh, N. et al., et al.

Gotoh, Laks, Nakashima, Lax, Schlessinger,

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High impact information on Frs2

Moreover, both the expression of Bmp4 in ExE and activation of Smad1/5 in epiblasts are reduced in Frs2alpha-null embryos [1].
In this study, we show that stimulation of C2C12 myoblasts with FGF-2 induces SHP-2 complex formation with tyrosyl-phosphorylated FGFR substrate 2 alpha (FRS-2 alpha) [2].
FGFR1-IIIb-expressing cells synthesized a glycosylated 110-kDa protein enhancing tyrosine phosphorylation of FGFR substrate-2 on FGF-1 stimulation [3].
To determine the developmental requirements for Fgfr1-Frs signaling, we generated mice (Fgfr1(Delta)Frs/DeltaFrs) in which the Frs2/3-binding site on Fgfr1 is deleted [4].
The signaling adapters fibroblast growth factor receptor substrate 2 and 3 are activated by the thyroid TRK oncoproteins [5].

Biological context of Frs2

Here we report that cell cycle inducer Cks1, which triggers ubiquitination and degradation of p27(Kip1), associates with the unphosphorylated form of FGFR substrate 2 (FRS2), an adaptor protein that is phosphorylated by FGFR kinases and recruits downstream signaling molecules [6].

Other interactions of Frs2

Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development [4].
We report that Frs2alpha and Frs2beta have distinct spatio-temporal expression patterns in mouse embryos [7].

References

The docking protein FRS2alpha is an essential component of multiple fibroblast growth factor responses during early mouse development. Gotoh, N., Manova, K., Tanaka, S., Murohashi, M., Hadari, Y., Lee, A., Hamada, Y., Hiroe, T., Ito, M., Kurihara, T., Nakazato, H., Shibuya, M., Lax, I., Lacy, E., Schlessinger, J. Mol. Cell. Biol. (2005) [Pubmed]
Role of SHP-2 in fibroblast growth factor receptor-mediated suppression of myogenesis in C2C12 myoblasts. Kontaridis, M.I., Liu, X., Zhang, L., Bennett, A.M. Mol. Cell. Biol. (2002) [Pubmed]
Identification of a fibroblast growth factor receptor 1 splice variant that inhibits pancreatic cancer cell growth. Liu, Z., Neiss, N., Zhou, S., Henne-Bruns, D., Korc, M., Bachem, M., Kornmann, M. Cancer Res. (2007) [Pubmed]
Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development. Hoch, R.V., Soriano, P. Development (2006) [Pubmed]
The signaling adapters fibroblast growth factor receptor substrate 2 and 3 are activated by the thyroid TRK oncoproteins. Ranzi, V., Meakin, S.O., Miranda, C., Mondellini, P., Pierotti, M.A., Greco, A. Endocrinology (2003) [Pubmed]
Direct cell cycle regulation by the fibroblast growth factor receptor (FGFR) kinase through phosphorylation-dependent release of Cks1 from FGFR substrate 2. Zhang, Y., Lin, Y., Bowles, C., Wang, F. J. Biol. Chem. (2004) [Pubmed]
FRS2 family docking proteins with overlapping roles in activation of MAP kinase have distinct spatial-temporal patterns of expression of their transcripts. Gotoh, N., Laks, S., Nakashima, M., Lax, I., Schlessinger, J. FEBS Lett. (2004) [Pubmed]

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FRS2	Bos taurus
FRS2	Canis lupus familiaris
frs2a	Danio rerio
FRS2	Gallus gallus
FRS2	Homo sapiens
LOC717117	Macaca mulatta
FRS2	Pan troglodytes
Frs2	Rattus norvegicus
frs2	Xenopus (Silurana) tropicalis

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