COMPETITIVE SIGNALING BETWEEN TRKA AND P75 NERVE GROWTH-FACTOR RECEPTORS DETERMINES CELL-SURVIVAL

In addition to its role as a survival factor, nerve growth factor (NGF ) has been implicated in initiating apoptosis in restricted cell types both during development and after terminal cell differentiation. NGF binds to the TrkA tyrosine kinase and the p75 neurotrophin receptor, a member of the tumor necrosis factor cytokine family. To understand th e mechanisms underlying survival versus death decisions, the TrkA rece ptor was introduced into oligodendrocyte cell cultures that undergo ap optosis in a p75-dependent manner. Here we report that activation of t he TrkA NGF receptor in oligodendrocytes negates cell death by the p75 receptor. TrkA-mediated rescue from apoptosis correlated with mitogen -activated protein kinase activation. Concurrently, activation of TrkA in oligodendrocytes resulted in suppression of c-jun kinase activity initiated by p75, whereas induction of NF kappa B activity by p75 was unaffected. These results indicate that TrkA-mediated rescue involves not only activation of survival signals but also simultaneous suppress ion of a death signal by p75. The selective interplay between tyrosine kinase and cytokine receptors provides a novel mechanism that achieve s alternative cellular responses by merging signals from different lig and-receptor systems.