Neutrophin Signalling

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TRK ligands (these ligands are most commonly nerve growth factor [NGF] for TRKA, brain-derived growth factor [BDGF] or neurotrophin 4 [NT-4] for TRKB, and neurotrophin 3 [NT-3] for TRKC) bind with high affinity to the extracellular domain of the TRK receptor. This leads to receptor dimerisation and autophosphorylation of specific tyrosine residues in the intracellular domain of TRK proteins [1, 2]. This results in activation of signal transduction pathways involved in proliferation, differentiation, and survival (e.g. MAPK, PI3K and PKC pathways) in both normal and neoplastic cells as shown below [1, 2].

Figure 2: TRK Receptor Signalling

Figure 2: TRK Receptor Signalling

With permission from Amatu et al. 2016 [1].

References

  1. Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open 2016; 1: e000023.
  2. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15: 731-747.

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Last update: 24 June 2019