Reactome | Activated NTRK2 signals through FRS2 and FRS3

Activated NTRK2 signals through FRS2 and FRS3

Stable Identifier

R-HSA-9028731

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Activated NTRK2 signals through FRS2 and FRS3

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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
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
10196222	Brain-derived neurotrophic factor induces phosphorylation of fibroblast growth factor receptor substrate 2 Middlemas, DS, Zhu, X, Moody, NM, Easton, JB	J. Biol. Chem.	1999
16697063	Trk receptor binding and neurotrophin/fibroblast growth factor (FGF)-dependent activation of the FGF receptor substrate (FRS)-3 Dixon, SJ, MacDonald, JI, Kubu, CJ, Meakin, SO, Robinson, KN	Biochim. Biophys. Acta	2006
24470253	Structural insights into FRS2α PTB domain recognition by neurotrophin receptor TrkB Zhou, MM, Mujtaba, S, Zeng, L, Kuti, M	Proteins	2014
10486198	Early BDNF, NT-3, and NT-4 signaling events Yuen, EC, Mobley, WC	Exp. Neurol.	1999