Activated NTRK2 signals through FRS2 and FRS3

Stable Identifier
R-HSA-9028731
Type
Pathway
Species
Homo sapiens
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Adapter proteins FRS2 and FRS3 can both bind to the cytoplasmic tail of activated NTRK2 (TRKB) receptor, which is followed by NTRK2-mediated phosphorylation of FRS2 and FRS3. NTRK2 signaling through FRS3 has been poorly characterized (Easton et al. 1999, Yuen and Mobley 1999, Dixon et al. 2006, Zeng et al. 2014). Phosphorylated FRS2 is known to recruit GRB2 (presumably in complex with SOS1) and PTPN11 (SHP2) to activated NTRK2, leading to augmentation of RAS signaling (Easton et al. 1999, Easton 2006).

Literature References
PubMed ID Title Journal Year
10196222 Brain-derived neurotrophic factor induces phosphorylation of fibroblast growth factor receptor substrate 2

Easton, JB, Moody, NM, Zhu, X, Middlemas, DS

J. Biol. Chem. 1999
16573649 The protein tyrosine phosphatase, Shp2, is required for the complete activation of the RAS/MAPK pathway by brain-derived neurotrophic factor

Easton, JB, Royer, AR, Middlemas, DS

J. Neurochem. 2006
16697063 Trk receptor binding and neurotrophin/fibroblast growth factor (FGF)-dependent activation of the FGF receptor substrate (FRS)-3

Dixon, SJ, MacDonald, JI, Robinson, KN, Kubu, CJ, Meakin, SO

Biochim. Biophys. Acta 2006
24470253 Structural insights into FRS2α PTB domain recognition by neurotrophin receptor TrkB

Zeng, L, Kuti, M, Mujtaba, S, Zhou, MM

Proteins 2014
10486198 Early BDNF, NT-3, and NT-4 signaling events

Yuen, EC, Mobley, WC

Exp. Neurol. 1999
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