PMID- 9753156 OWN - NLM STAT- MEDLINE DCOM- 19981022 LR - 20190815 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 10 IP - 3 DP - 1998 Mar TI - Reciprocal modulation of TrkA and p75NTR affinity states is mediated by direct receptor interactions. PG - 890-8 AB - Equilibrium binding of 125I-nerve growth factor (125I-NGF) to cells coexpressing the tyrosine kinase receptor A (TrkA) and common neurotrophin receptor (p75NTR), cells coexpressing both receptors where p75NTR is occupied, and cells expressing only p75NTR, revealed reciprocal modulation of receptor affinity states. Analysis of receptor affinity states in PC12 cells, PC12 cells in the presence of brain-derived neurotrophic factor (BDNF), and PC12nnr5 cells suggested that liganded and unliganded p75NTR induce a higher affinity state within TrkA, while TrkA induces a lower affinity state within p75NTR. These data are consistent with receptor allosterism, and prompted a search for TrkA/p75NTR complexes in the absence of NGF. Chemical crosslinking studies revealed high molecular weight receptor complexes that specifically bound 125I-NGF, and were immunoprecipitated by antibodies to both receptors. The heteroreceptor complex of TrkA and p75NTR alters conformation and/or dissociates in the presence of NGF, as indicated by the ability of low concentrations of NGF to prevent heteroreceptor crosslinking. These data suggest a new model of receptor interaction, whereby structural changes within a heteroreceptor complex are induced by ligand binding. FAU - Ross, G M AU - Ross GM AD - Department of Medicine, Kingston General Hospital, Ontario, Canada. FAU - Shamovsky, I L AU - Shamovsky IL FAU - Lawrance, G AU - Lawrance G FAU - Solc, M AU - Solc M FAU - Dostaler, S M AU - Dostaler SM FAU - Weaver, D F AU - Weaver DF FAU - Riopelle, R J AU - Riopelle RJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cross-Linking Reagents) RN - 0 (Ligands) RN - 0 (Nerve Growth Factors) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Receptor, Nerve Growth Factor) RN - 0 (Receptors, Nerve Growth Factor) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkA) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cross-Linking Reagents MH - Ligands MH - Models, Neurological MH - Molecular Weight MH - Nerve Growth Factors/metabolism MH - PC12 Cells MH - Phosphorylation MH - Precipitin Tests MH - Proto-Oncogene Proteins/chemistry/*metabolism MH - Rats MH - Receptor Protein-Tyrosine Kinases/chemistry/*metabolism MH - Receptor, Nerve Growth Factor MH - Receptor, trkA MH - Receptors, Nerve Growth Factor/chemistry/*metabolism MH - Signal Transduction/physiology EDAT- 1998/09/30 00:00 MHDA- 1998/09/30 00:01 CRDT- 1998/09/30 00:00 PHST- 1998/09/30 00:00 [pubmed] PHST- 1998/09/30 00:01 [medline] PHST- 1998/09/30 00:00 [entrez] AID - 10.1046/j.1460-9568.1998.00094.x [doi] PST - ppublish SO - Eur J Neurosci. 1998 Mar;10(3):890-8. doi: 10.1046/j.1460-9568.1998.00094.x.