Disruption of NGF binding to the low affinity neurotrophin receptor p75LNTR reduces NGF binding to TrkA on PC12 cells.
The role of the low affinity neurotrophin receptor, p75LNTR, in NGF-mediated signal transduction has been examined. Our results show that treatment of PC12 cells with MC192, a monoclonal antibody directed against p75LNTR, results in reduced NGF binding to TrkA and attenuated TrkA activation. Use of mutant NGF that binds TrkA but not p75LNTR shows that the MC192 effect requires that NGF bind the p75LNTR receptor. To explore the possibility that MC192 disrupts some normal functional role of p75LNTR, BDNF was used to block binding of NGF to p75LNTR on PC12 cells. By preventing NGF binding to p75LNTR, NGF binding to TrkA and NGF-mediated signal transduction were reduced. We propose that p75LNTR normally acts to increase binding of NGF to TrkA, possibly by increasing the local NGF concentration in the microenvironment surrounding the cell surface TrkA receptor.
Barker
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Department of Neurobiology, Stanford University, California 94305-5401.
Shooter
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D001667:Binding, Competitive; D019208:Brain-Derived Neurotrophic Factor; D016762:Genes, fos; D007163:Immunosorbent Techniques; D008969:Molecular Sequence Data; D009154:Mutation; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D016716:PC12 Cells / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA