p75 reduces TrkB tyrosine autophosphorylation in response to brain-derivedneurotrophic factor and neurotrophin 4/5

Neurotrophins mediate their signals through two different receptors: the fa mily of receptor tyrosine kinases, Trks, and the low affinity pan-neurotrop hin receptor p75. Trk receptors show more restricted ligand specificity, wh ereas all neurotrophins are able to bind to p?5, One important function of p75 is the enhancement of nerve growth factor signaling via TrkA by increas ing TrKA tyrosine autophosphorylation. Here, we have examined the importanc e of p75 on TrkB- and TrkC-mediated neurotrophin signaling in an MG87 fibro blast cell line stably transfected with either p75 and TrkB or p75 and TrkC , as well as in PC12 cells stably transfected with TrkB. In contrast to Trk A signaling, p75 had a negative effect on TrkB tyrosine autophosphorylation in response to its cognate neurotrophins, brain-derived neurotrophic facto r and neurotrophin 4/5. On the other hand, p75 had no effect on TrkB or Trk C activation in neurotrophin 3 treatment. p75 did not effect extracellular signal-regulated kinase 2 tyrosine phosphorylation in response to brain-der ived neurotrophic factor, neurotrophin 3, or neurotrophin 4/5. These result s suggest that the observed reduction in TrkB tyrosine autophosphorylation caused by p75 does not influence Ras/mitogen-activated protein kinase signa ling pathway in neurotrophin treatments.