p75(NGFR)and TrkA receptors collaborate to rapidly activate a p75(NGFR)-associated protein kinase

The role of the low affinity nerve growth factor receptor (p75(NGFR)) in NGF-mediated signaling is not yet understood, Here we show by co-immunoprecipitation that NGF activates a protein kinase that is directly associated with p75(NGFR) in dorsal root ganglion (DRG) cells and PC12 cells in culture. Two proteins of 120 and 104 kDa constitute the majority of this activity. In PC12 cells, TrkA activation was necessary to elicit p75(NGFR)-associated kinase activity. Although NGF binding to p75(NGFR) was not necessary for kinase activation, it accelerated the activation of the kinase at low NGF concentrations. Deletion analysis showed that a 43 amino acid region in the cytoplasmic domain of p75(NGFR) was responsible for this effect, These findings show that p75(NGFR) accelerates TrkA-mediated signaling and, in addition, demonstrate that p75(NGFR) and TrkA collaborate to activate a previously undescribed p75(NGFR)-associated protein kinase.