Neurotrophin signaling via Trks and p75

This review focuses on recent advances in our understanding of receptor-med iated signaling by the neurotrophins NGF, BDNF, NT3, and NT4/5. Two distinc t receptor types have been distinguished, Trks and p75. The Trks are recept or tyrosine kinases that utilize a complex set of substrates and adapter pr oteins to activate defined secondary signaling cascades required for neurot rophin-promoted neuronal differentiation, plasticity, and survival. A speci alized aspect of Trk/neurotrophin action in neurons is the requirement for retrograde signaling from the distal periphery to the cell body. p75 is a u niversal receptor for neurotrophins that is a member of the TNF receptor/Fa s/CD40 superfamily, p75 appears to modify Trk signaling when the two recept or types are coexpressed. When expressed in the absence of Trks, p75 mediat es responses to neurotrophins including promotion of apoptotic death. The m echanisms of p75 receptor signaling remain to be fully understood. (C) 1999 Academic Press.