Figure 1

Trk receptor activation by neurotrophic factors. Binding of neurotrophic factor causes dimerization and autophosphorylation of the receptor leading to activation of signaling cascades through Src and Shc adaptor proteins which bind the Trk. Once activated Shc increases the activation of Ras, which leads to MAPK/ERK1/2, causing differentiation and survival through transcriptional events, an event that can also occur in signaling endosomes. Shc activation also leads to increases in Akt through activation of PI3K promoting cell survival by inhibiting apoptotic signaling. NT: neurotrophin; Trk: tyrosine kinase receptor; ERK1/2: extracellular signal-regulated kinase; MEK: mitogen-activated protein kinase; PLC-γ: phospholipase Cγ; rap1: ras-related protein1; Shp2: tyrosine phosphatases.