Dual role for p75^NTR 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.

PTPL1: a large phosphatase with a split personality

“…The mechanisms of p75 NTR function in the modulation of cell death signaling are somewhat confused and require resolution [54,55]. Tyrosine phosphorylation of p75 NTR induces its ubiquitination [56] and its potential proteosomal degradation, while dephosphorylation of p75 NTR by PTPL1 may stabilize the protein leading to an increase in its intracellular level, thus promoting cell survival.…”

Polarity proteins PAR6 and aPKC regulate cell death through GSK-3β in 3D epithelial morphogenesis

“…P62/ZIP, another protein that interacts with the N-terminus of aPKC, has been shown to recruit aPKC into a TNF-␣ receptor complex and an NGF receptor complex, transducing signals for cell survival (Mamidipudi and Wooten, 2002;Sanz et al, 1999). PKC has also been described to protect cells against FasL-induced apoptosis in Jurkat cells (Leroy et al, 2005).…”

Thyroid Hormone Enhances Neurite Outgrowth in Neuroscreen 1 Cells

“…Binding of NGF to the TrkA receptor is what stimulates signal transduction pathways mediating most of the survival and growth effects of NGF, including neurite outgrowth [46]. Binding of NGF to the p75NTR receptor mainly leads to a positive modulation of the NGF/TrkA binding, but p75NTR activation could also cause apoptosis depending on the type of protein interacting with the receptor [46][47][48][49][50][51][52].…”