ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: The β-amyloid protein (Aβ) peptide plays an important role in Alzheimer's disease, but the potential actions of physiologic levels of Aβ (225–625 pM) have not been explored. We recently showed that picomolar doses of Aβ can stimulate tyrosine phosphorylation of neuronal cells and now show that leads to the activation of the lipid kinase phosphatidylinositol 3-kinase (PI3 kinase). Three independent lines of evidence support the hypothesis that Aβ is activating PI3 kinase through a tyrosine kinase-mediated mechanism. Immunoblotting studies show that Aβ induces tyrosine phosphorylation of p85 as well as association of the p85 subunit of PI3 kinase with tyrosine-phosphorylated proteins. Studies of membrane proteins show that Aβ induces a translocation of p85 to membrane-bound glycoproteins, which are likely to be receptors. Finally, direct studies of PI3 kinase activity in both anti-phosphotyrosine immunocomplexes and wheat germ agglutinin precipitates show that Aβ increases formation of the product of PI3 kinase. Wortmannin, a selective inhibitor of PI3 kinase, blocks this Aβ-stimulated PI3 kinase activity. Thus, physiologic levels of Aβ stimulate tyrosine phosphorylation and PI3 kinase activity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1996.67030978.x
Permalink
