Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor.
The role of the low-affinity neurotrophin receptor (p75NTR) in signal transduction is undefined. Nerve growth factor can activate the sphingomyelin cycle, generating the putative-lipid second messenger ceramide. In T9 glioma cells, addition of a cell-permeable ceramide analog mimicked the effects of nerve growth factor on cell growth inhibition and process formation. This signaling pathway appears to be mediated by p75NTR in T9 cells and NIH 3T3 cells overexpressing p75NTR. Expression of an epidermal growth factor receptor-p75NTR chimera in T9 cells imparted to epidermal growth factor the ability to activate the sphingomyelin cycle. These data demonstrate that p75NTR is capable of signaling independently of the trk neurotrophin receptor (p140trk) and that ceramide may be a mediator in neurotrophin biology.
Dobrowsky
R T
RT
Departments of Medicine and Cell Biology, Duke University Medical Center, Durham, NC 27710.
Werner
M H
MH
Castellino
A M
AM
Chao
M V
MV
Hannun
Y A
YA
D016475:3T3 Cells; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002518:Ceramides / Q000378:metabolism / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005909:Glioblastoma; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013109:Sphingomyelins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002518:Ceramides; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D013109:Sphingomyelins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA