NERVE GROWTH-FACTOR BINDS TO THE 140 KD TRK PROTOONCOGENE PRODUCT AND STIMULATES ITS ASSOCIATION WITH THE SRC HOMOLOGY DOMAIN OF PHOSPHOLIPASE-C-GAMMA-1

The cellular actions of nerve growth factor (NGF) involve regulation of protein phosphorylation. In PC-12 pheochromocytoma cells, exposure of [125I]NGF followed by crosslinking indicates that the ligand binds to two discreet receptors, the previously described 75 kd protein, as well as the trk proto-oncogene product pp140c-trk. Competition experiments reveal that of the two, pp140c-trk binds to NGF with higher affinity. Following exposure to NGF, pp140c-trk undergoes a rapid autophosphorylation on tyrosine residues, and concomitantly phosphorylates and associates with phospholipase Cγ1 (PLCγ1), through interaction with its src homology domains. The binding of NGF to pp140c-trk with high affinity, the NGF-dependent activation of its tyrosine kinase activity and the specific association with the effector molecule, PLCγ1, suggests that this is the biologically relevant signaling receptor for NGF. © 1991.