Pathway
Signaling by NTRK3 (TRKC)
NTRK3 (TRKC) belongs to the family of neurotrophin receptor tyrosine kinases, which also includes NTRK1 (TRKA) and NTRK2 (TRKB). Neurotrophin-3 (NTF3, also known as NT-3) is the ligand for NTRK3. Similar to other NTRK receptors and receptor tyrosine kinases in general, ligand binding induces receptor dimerization followed by trans-autophosphorylation on conserved tyrosines in the intracellular (cytoplasmic) domain of the receptor. These conserved tyrosines serve as docking sites for adaptor proteins that trigger downstream signaling cascades. Signaling through PLCG1, PI3K and RAS, downstream of activated NTRK3, regulates cell survival, proliferation and motility.
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In the absence of its ligand, NTRK3 functions as a dependence receptor and triggers BAX and CASP9-dependent cell death.
NTRK3 was reported to activate STAT3 through JAK2, but the exact mechanism has not been elucidated. NTRK3 was reported to interact with the adaptor protein SH2B2, but the biological role of this interaction has not been determined.
Receptor protein tyrosine phosphatases PTPRO and PTPRS (PTPsigma) negatively regulate NTRK3 signaling by dephosphorylating NTRK3. In addition to dephosphorylation of NTRK3 in-cis, the extracellular domain of pre-synaptic PTPRS can bind in-trans to extracellular domain of post-synaptic NTRK3, contributing to synapse formation.
What the reference databases state
Statements
14 statements
14 statements · 1 reference database · Subject: Signaling by NTRK3 (TRKC) · Sources: Reactome
- BAX participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- HRAS participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- IRS1 participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- NELFB participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- NRAS participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- NTF3 participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- NTRK3 participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- PIK3CA participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- PIK3R1 participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- PLCG1 participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- PTPRO participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- PTPRS participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
Show the remaining 2
- SOS1 participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only
- SRC participates in Signaling by NTRK3 (TRKC)ProteinReactome R-HSA-9034015Inferred only