Activated NTRK2 signals through FYN

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R-HSA-9032500
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Pathway
Species
Homo sapiens
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In mouse brain, Fyn activation downstream of Bdnf-induced Ntrk2 (TrkB) signaling results in increased protein levels of AMPA receptor subunits Gria2 (GluR2), Gria3 (GluR3) and Gria1 (GluR1) without change in mRNA levels (Narisawa-Saito et al. 1999).

BDNF-mediated activation of NTRK2 increases phosphorylation of voltage gated sodium channels by FYN, resulting in decrease of sodium currents (Ahn et al. 2007).

FYN activation downstream of NTRK2 is implicated in olygodendrocyte myelination and contributes to BDNF-induced activation of ERK1/2 (MAPK3/1) through an unknown mechanism (Peckham et al. 2015).

Besides acting downstream of NTRK2, FYN and other SRC kinases, activated by other receptors such as GPCRs, may phosphorylate NTRK2 and enhance its catalytic activity (Rajagopal and Chao 2006, Huang and McNamara 2010).

Literature References
PubMed ID Title Journal Year
26449489 Fyn is an intermediate kinase that BDNF utilizes to promote oligodendrocyte myelination

Peckham, H, Giuffrida, L, Wood, R, Gonsalvez, D, Ferner, A, Kilpatrick, TJ, Murray, SS, Xiao, J

Glia 2016
12663749 Involvement of BDNF receptor TrkB in spatial memory formation

Mizuno, M, Yamada, K, He, J, Nakajima, A, Nabeshima, T

Learn. Mem. 2003
17959796 Regulation of Na(v)1.2 channels by brain-derived neurotrophic factor, TrkB, and associated Fyn kinase

Ahn, M, Beacham, D, Westenbroek, RE, Scheuer, T, Catterall, WA

J. Neurosci. 2007
10051665 Growth factor-mediated Fyn signaling regulates alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression in rodent neocortical neurons

Narisawa-Saito, M, Silva, AJ, Yamaguchi, T, Hayashi, T, Yamamoto, T, Nawa, H

Proc. Natl. Acad. Sci. U.S.A. 1999
20064930 Mutual regulation of Src family kinases and the neurotrophin receptor TrkB

Huang, YZ, McNamara, JO

J. Biol. Chem. 2010
16860569 A role for Fyn in Trk receptor transactivation by G-protein-coupled receptor signaling

Rajagopal, R, Chao, MV

Mol. Cell. Neurosci. 2006
9648856 Association of the Src family tyrosine kinase Fyn with TrkB

Iwasaki, Y, Gay, B, Wada, K, Koizumi, S

J. Neurochem. 1998
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