Dual role for p75NTR signaling in survival and cell death: Can intracellular mediators provide an explanation?

Abstract

Several recent reports support a dual role of p75^NTR in cell death, as well as survival, depending on the physiological or developmental stage of the cells. Coexpression of the TrkA receptor with p75^NTR further enhances the complexity of nerve growth factor (NGF) signaling. Recent identification of serine/threonine kinases that interact with the p75^NTR provides an explanation for the lack of an apparent kinase domain needed for signaling. In this report, we review the possible roles of the intracellular proteins that directly interact with the p75^NTR, atypical protein kinase C (PKC) binding protein, p62 and second messengers in the functional antagonism exhibited by TrkA and p75^NTR with an emphasis on the nuclear factor‐kappa B activation pathway.