Direct interaction of soluble human recombinant tau protein with Abeta 1-42 results in tau aggregation and hyperphosphorylation by tau protein kinase II.
We report here that aggregated beta-amyloid (Abeta) 1-42 promotes tau aggregation in vitro in a dose-dependent manner. When Abeta-mediated aggregated tau was used as a substrate for tau protein kinase II (TPK II), an 8-fold increase in the rate of TPK II-mediated tau phosphorylation was observed. The extent of TPK II-dependent tau phosphorylation increased as a function of time and Abeta 1-42 concentration, and hyperphosphorylated tau was found to be decorated with an Alzheimer's disease-related phosphoepitope (P-Thr-231). In HEK 293 cells co-expressing CT-100 amyloid precursor protein and tau, the release of Abeta 1-42 from these cells was impaired. Taken together, these in vitro results suggest that Abeta 1-42 promotes both tau aggregation and hyperphosphorylation.
Rank
Kenneth B
KB
Protein Science, 7240-267-117, Pharmacia Corporation, Kalamazoo, MI 49007, USA.
Pauley
Adele M
AM
Bhattacharya
Keshab
K
Wang
Zhigang
Z
Evans
David B
DB
Fleck
Timothy J
TJ
Johnston
Jennifer A
JA
Sharma
Satish K
SK
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002460:Cell Line; D051360:Cyclin-Dependent Kinase 5; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D046911:Macromolecular Substances; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012995:Solubility / Q000187:drug effects; D016875:tau Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000939:Epitopes; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C079134:tau protein kinase II