Amyloid precursor protein modulates the interaction of nerve growth factor with p75 receptor and potentiates its activation of trkA phosphorylation.
We have recently shown that the secreted form of amyloid precursor protein (APPs) potentiates the neurotrophic actions of nerve growth factor (NGF). The combined presence of NGF and APPs in low concentrations resulted in a synergistic potentiation of NGF neuritogenic activity on PC12 cells. Therefore, the effect of APPs on NGF receptor-binding has been examined. In the presence of APPs, the apparent affinity of NGF's low affinity binding site increased by a factor of 2.5. In addition, a 2- to 2.5-fold decrease in the number of sites was observed, although APPs did not compete with NGF for the same binding sites. These effects of APPs were not caused by direct interaction with NGF itself. In addition, APPs synergistically potentiated the tyrosine phosphorylation of trkA due to NGF. These results suggest that an increased affinity of p75 for NGF may underlie the potentiation of neurotrophic actions of NGF by APPs, and that increase may be caused by an indirect interaction between APPs and p75.
Akar
C A
CA
Laboratory of Cellular and Molecular Biology, National Institute on Aging, Gerontology Research Center, 4940 Eastern Ave., Baltimore, MD 21224, USA.
Wallace
W C
WC
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000166:cytology; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism* / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA