TrkA, apparent molecular weight 140 kDa, is a high affinity nerve growth factor (NGF). The Trk proto-oncogene family contains four members, TrkA, TrkB, TrkC, and TrkE, which are variably expressed throughout the central and peripheral nervous systems. TrkA binds to nerve growth factor (NGF) and autophosphorylates on tyrosine residues (Tyr490, Tyr674, Tyr675, Tyr751 and Tyr785) to activate multiple downstream effector proteins. Phosphorylation at Tyr490 is required for Shc association and subsequent activation of the Ras-MAP kinase-signaling cascade, which leads to activation of Elk-1-dependent gene transcription and neurite growth. Phosphorylations at Tyr674 and Tyr675 lie within the catalytic domain of TrkA tyrosine kinase and reflect Trk kinase activity. Additionally, phosphorylation at Tyr751 is required for PI3-kinase association and activation of the Akt signaling cascade.