RT Journal Article
SR Electronic
T1 A Protein Kinase, PKN, Accumulates in Alzheimer Neurofibrillary Tangles and Associated Endoplasmic Reticulum-Derived Vesicles and Phosphorylates Tau Protein
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7402
OP 7410
DO 10.1523/JNEUROSCI.18-18-07402.1998
VO 18
IS 18
A1 Toshio Kawamata
A1 Taizo Taniguchi
A1 Hideyuki Mukai
A1 Michinori Kitagawa
A1 Takeshi Hashimoto
A1 Kiyoshi Maeda
A1 Yoshitaka Ono
A1 Chikako Tanaka
YR 1998
UL http://www.jneurosci.org/content/18/18/7402.abstract
AB A possible role for a protein kinase, PKN, a fatty acid-activated serine/threonine kinase with a catalytic domain homologous to the protein kinase C family and a direct target for Rho, was investigated in the pathology of Alzheimer’s disease (AD) using a sensitive immunocytochemistry on postmortem human brain tissues and a kinase assay for human tau protein. The present study provides evidences by light, electron, and confocal laser microscopy that in control human brains, PKN is enriched in neurons, where the kinase is concentrated in a subset of endoplasmic reticulum (ER) and ER-derived vesicles localized to the apical compartment of juxtanuclear cytoplasm, as well as late endosomes, multivesicular bodies, Golgi bodies, secretary vesicles, and nuclei. In AD-affected neurons, PKN was redistributed to the cortical cytoplasm and neurites and was closely associated with neurofibrillary tangles (NFTs) and their major constituent, abnormally modified tau. PKN was also found in degenerative neurites within senile plaques. In addition, we report that human tau protein is directly phosphorylated by PKN both in vitro and in vivo. Thus, our results suggest a specific role for PKN in NFT formation and neurodegeneration in AD damaged neurons.