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Activation of the mitogen‐activated protein kinase pathway through p75 NTR : A common mechanism for the neurotrophin family
Author(s) -
Lad Shivanand P.,
Neet Kenneth E.
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10695
Subject(s) - trk receptor , mapk/erk pathway , neurotrophin , low affinity nerve growth factor receptor , microbiology and biotechnology , protein kinase a , mitogen activated protein kinase , biology , receptor tyrosine kinase , signal transduction , receptor , kinase , receptor protein tyrosine kinases , biochemistry
Abstract Neurotrophins interact with two distinct classes of cell‐surface receptors, the Trk receptor tyrosine kinase family and the common neurotrophin receptor p75 NTR . For many years, the biological role of p75 NTR remained obscure, being relegated to modulating Trk binding of neurotrophins. Recently, the importance of p75 NTR as a signaling receptor in itself has become increasingly clear. The signals initiated by p75 NTR are likely to be as complex as those for the Trk family and probably depend on the cell system in which such signaling is being studied. In this study, all members of the neurotrophin family were demonstrated to be capable of stimulating p75 NTR ‐mediated activation of the mitogen‐activated protein kinase (MAPK) family (ERK1,2). This activation is rapid and transient, peaking at 5–15 min, depending on the cell system. The classical MAPK cascade consists of the reaction series Ras‐Raf‐MEK‐MAPK. The p75 NTR ‐induced MAPK activation is MEK dependent but Raf independent. This result implies that neurotrophin activation of p75 NTR results in some cascade (as yet unknown) that bypasses Raf and converges on MEK to result in activation of MAPK. This activated MAPK is then able to translocate to the nucleus. The effect of this MAPK activation on cell survival is dependent on cell type. These results support the concept that signaling from the p75 NTR receptor is more diverse and extensive than previously believed. © 2003 Wiley‐Liss, Inc.