Trks: Signal transduction and intracellular pathways

The neurotrophin family of growth factors supports survival and differentiation of neurons in the developing vertebrate nervous system by binding activating receptor tyrosine kinases, the Trks. Activation of Trk receptors leads to stimulation of a number of intracellular signaling cascades including, among others, the ras/extracellular regulated kinase (erk) and the phosphatidylinositol-3 kinase (PI 3 kinase) cascades. Over the past several years, work in several neurotrophin responsive systems has begun to identify the role each of these signaling cascades plays in the cellular response to neurotrophins. It now appears that neurotrophins, in particular nerve growth factor (NGF), mediate their multiple effects through a number of distinct intracellular signaling cascades. In this review, we will overview the evidence implicating specific signaling cascades in aspects of the cellular response to the neurotrophins, specifically in response to activation of TrkA by NGF.