title: TrkA and mitogen-activated protein kinase phosphorylation are enhanced in sympathetic neurons lacking functional p75 neurotrophin receptor expression.
abstract: This study examined the effects of hypomorphic p75 neurotrophin receptor (p75NTR) expression and high levels of nerve growth factor (NGF) on trkA phosphorylation and downstream activation of p44/42 mitogen-activated protein kinase (MAPK). Post-ganglionic sympathetic neurons from postnatal day 1 p75NTR exon III null mutant (p75(-/-)) and 129/SvJ mice were cultured in the presence of 50 ng/mL NGF and analysed by Western blotting. Levels of phosphorylated trkA are increased in p75(-/-) neurons compared with 129/SvJ neurons, and these higher levels are maintained with continuous exposure to NGF. MAPK is also phosphorylated to a greater extent in p75(-/-) neurons than in 129/SvJ neurons, both within 10 min of exposure to NGF, and with continuous NGF treatment for 5 days. These data provide new insight into the mechanism underlying enhanced neurite outgrowth in p75(-/-) neurons, demonstrating that trkA and MAPK signalling in sympathetic neurons are increased when p75NTR function is disrupted.
authors.affiliation: Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Sari S
authors.initials: SS
authors.lastname: Hannila
authors.forename: Gail M
authors.initials: GM
authors.lastname: Lawrance
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Ross
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kawaja
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002352:Carrier Proteins / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests / Q000379:methods; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology*; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020928:Mitogen-Activated Protein Kinases