Dual role for p75(NTR) signaling in survival and cell death: can intracellular mediators provide an explanation?

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. Copyright 2002 Wiley-Liss, Inc.