Activated NTRK2 signals through CDK5

Stable Identifier
R-HSA-9032845
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Pathway
Species
Homo sapiens
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CDK5, in complex with its activator CDK5R1 (p35), binds to BDNF-activated NTRK2 (TRKB). NTRK2 promotes CDK5 catalytic activity by phosphorylating CDK5 at tyrosine residue Y15 (Cheung et al. 2007), although CDK5 can also be phosphorylated at Y15 independently of NTRK2 (Zhao et al. 2009). CDK5 phosphorylates serine residue S479 of NTRK2 (corresponds to S478 in mouse and rat) (Cheung et al. 2007, Zhao et al. 2009). Phosphorylation of NTRK2 at S479 is needed for BDNF-triggered dendritic growth (Cheung et al. 2007), hippocampal long-term potentiation (LTP) and spatial memory (Lai et al. 2012). These processes involve NTRK2-mediated activation of RHO GTPases RAC1 (Lai et al. 2012) and possibly CDC42 (Cheung et al. 2007). In cultured isolated neurons, phosphorylation at S479 affects localization of NTRK2 (Zhao et al. 2009), but this does not appear to be the case in vivo (Lai et al. 2012).

CDK5-mediated phosphorylation of NTRK2 was suggested to influence the level of AKT activity, downstream mTOR signaling and DLG4 (PSD-95) expression, but further elucidation is needed (Lai et al. 2012).

Signaling by TRKB and CDK5 plays a role in inflammation induced hypersensitivity to heat-triggered pain in rats (Zhang et al. 2014).

Literature References
PubMed ID Title Journal Year
17341134 Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons

Cheung, ZH, Chin, WH, Chen, Y, Ng, YP, Ip, NY

PLoS Biol. 2007
23064382 TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory

Lai, KO, Wong, AS, Cheung, MC, Xu, P, Liang, Z, Lok, KC, Xie, H, Palko, ME, Yung, WH, Tessarollo, L, Cheung, ZH, Ip, NY

Nat. Neurosci. 2012
24465591 The BDNF/TrkB signaling pathway is involved in heat hyperalgesia mediated by Cdk5 in rats

Zhang, HH, Zhang, XQ, Xue, QS, Yan-Luo, -, Huang, JL, Zhang, S, Shao, HJ, Lu, H, Wang, WY, Yu, BW

PLoS ONE 2014
19671665 Mechanism underlying activity-dependent insertion of TrkB into the neuronal surface

Zhao, L, Sheng, AL, Huang, SH, Yin, YX, Chen, B, Li, XZ, Zhang, Y, Chen, ZY

J. Cell. Sci. 2009
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