Reactome | SHC-mediated cascade:FGFR4

SHC-mediated cascade:FGFR4

Stable Identifier

R-HSA-5654719

Type

Pathway

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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The exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction with the receptor has not been demonstrated. Co-precipitation of p46 and p52 with the FGFR2 IIIc receptor has been reported, but this interaction is thought to be indirect, possibly mediated by SRC. Consistent with this, co-precipitation of SHC1 and FGFR1 IIIc is seen in mammalian cells expressing v-SRC. The p66 isoform of SHC1 has also been co-precipitated with FGFR3, but this occurs independently of receptor stimulation, and the p66 isoform not been shown to undergo FGF-dependent phosphorylation. SHC1 has been shown to associate with GRB2 and SOS1 in response to FGF stimulation, suggesting that the recruitment of SHC1 may contribute to activation of the MAPK cascade downstream of FGFR.

Literature References

PubMed ID	Title	Journal	Year
9480847	Novel recruitment of Shc, Grb2, and Sos by fibroblast growth factor receptor-1 in v-Src-transformed cells Frankel, P, Foster, DA, Curto, M, Carrero, A	Biochem Biophys Res Commun	1998
8264585	Fibroblast growth factor receptors have different signaling and mitogenic potentials Wang, JK, Goldfarb, M, Gao, G	Mol Cell Biol	1994
9045692	Signal transduction pathway of human fibroblast growth factor receptor 3. Identification of a novel 66-kDa phosphoprotein. Podolsky, DK, Goke, M, Tsunekawa, S, Kanai, M	J Biol Chem	1997
15863030	Cellular signaling by fibroblast growth factor receptors Schlessinger, J, Eswarakumar, VP, Lax, I	Cytokine Growth Factor Rev	2005
18840094	Indirect recruitment of the signalling adaptor Shc to the fibroblast growth factor receptor 2 (FGFR2) Suhling, K, Levitt, JA, Ladbury, JE, Suen, KM, Ahmed, Z, Schüller, AC	Biochem J	2008