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-im munoprecipitation that NGF activates a protein kinase that is directly associated with p75(NGFR) in dorsal root ganglion (DRG) cells and PC1 2 cells in culture. Two proteins of 120 and 104 kDa constitute the maj ority of this activity. In PC12 cells, TrkA activation was necessary t o 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(N GFR) was responsible for this effect, These findings show that p75(NGF R) accelerates TrkA-mediated signaling and, in addition, demonstrate t hat p75(NGFR) and TrkA collaborate to activate a previously undescribe d p75(NGFR)-associated protein kinase.