RGD Reference Report - Activation of the mitogen-activated protein kinase pathway through p75NTR: a common mechanism for the neurotrophin family. - Rat Genome Database

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Activation of the mitogen-activated protein kinase pathway through p75NTR: a common mechanism for the neurotrophin family.

Authors: Lad, SP  Neet, KE 
Citation: Lad SP and Neet KE, J Neurosci Res. 2003 Sep 1;73(5):614-26.
RGD ID: 5508773
Pubmed: PMID:12929129   (View Abstract at PubMed)
DOI: DOI:10.1002/jnr.10695   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of MAPK cascade  IDA 5508773 RGD 
regulation of response to biotic stimulus  IDA 5508773neurotrophin-induced cell deathRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ngfr  (nerve growth factor receptor)


Additional Information