The Trk oncogene encodes a membrane-spanning protein tyrosine kinase, gp140Trk, whose expression is restricted in vivo to neurons of the sensory spinal and cranial ganglia of neural crest origin. Nerve growth factor (NGF) stimulates tyrosine phosphorylation of Trk A in neural cell lines and in embryonic dorsal root ganglia. Tyrosine phosphorylation of Trk by NGF is rapid, specific and occurs with picomolar quantities of factor, indicating that the response is mediated by physiological amounts of NGF, suggesting that Trk A participates in the primary signal transduction mechanism of NGF. An additional component of the Trk A receptor complex, NGFR p75, binds to the neurotrophic factors with low affinity but is required for efficient signaling. NGFR p75 accelerates Trk A activation and may recruit downstream effector molecules to the liganded complex.
