p75NTR and apoptosis: Trk-dependent and Trk-independent effects.
The ongoing dissection of the roles of p75NTR and TrkA, -B and -C in neurotrophin signaling has generated a number of apparent paradoxes. Limiting consideration to the role of p75NTR in cell death, a theory is proposed that is based on the following postulates: (1) that p75NTR displays a pro-apoptotic intrinsic (ligand-independent, Trk-independent) receptor effect (IRE), which is inhibited by ligand binding; (2) that p75NTR and TrkA exhibit mutual repression of signaling; and (3) that p75NTR and TrkA are required for the efficient generation of high-affinity NGF binding sites.
Bredesen
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DE
Burnham Institute, La Jolla, CA 92037, USA.
Rabizadeh
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S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D008959:Models, Neurological; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*
D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA