SELECTIVITY IN NEUROTROPHIN SIGNALING: Theme and Variations

Neurotrophins are a family of growth factors critical for the development and functioning of the nervous system. Although originally identified as neuronal survival factors, neurotrophins elicit many biological effects, ranging from proliferation to synaptic modulation to axonal pathfinding. Recent data indicate that the nature of the signaling cascades activated by neurotrophins, and the biological responses that ensue, are specified not only by the ligand itself but also by the temporal pattern and spatial location of stimulation. Studies on neurotrophin signaling have revealed variations in the Ras/MAP kinase, PI3 kinase, and phospholipase C pathways, which transmit spatial and temporal information. The anatomy of neurons makes them particularly appropriate for studying how the location and tempo of stimulation determine the signal cascades that are activated by receptor tyrosine kinases such as the Trk receptors. These signaling variations may represent a general mechanism eliciting specificity in growth factor responses.