Casein Kinase 1 Is Tightly Associated with Paired-Helical Filaments Isolated from Alzheimer's Disease Brain
Article first published online: 18 NOV 2002
Journal of Neurochemistry
Volume 69, Issue 6, pages 2506–2515, December 1997
How to Cite
Kuret, J., Johnson, G. S., Cha, D., Christenson, E. R., DeMaggio, A. J. and Hoekstra, M. F. (1997), Casein Kinase 1 Is Tightly Associated with Paired-Helical Filaments Isolated from Alzheimer's Disease Brain. Journal of Neurochemistry, 69: 2506–2515. doi: 10.1046/j.1471-4159.1997.69062506.x
- Issue published online: 18 NOV 2002
- Article first published online: 18 NOV 2002
- Received July 2, 1997; revised manuscript received August 7, 1997; accepted August 7, 1997.
- Alzheimer's disease;
- Neurofibrillary tangles;
- Paired-helical filaments;
- Tau protein;
- Protein phosphorylation;
- Casein kinase 1
Abstract: The protein kinase activity tightly associated with paired helical filaments (PHFs) purified from the brain tissue of individuals with Alzheimer's disease has been characterized in vitro. The activity is shown to phosphorylate casein, an exogenous substrate, with a maximal velocity of ∼2 nmol/min/mg, suggesting it comprises a significant component of the total protein in the PHF preparation. On the basis of substrate selectivity, isoquinoline sulfonamide inhibitor selectivity, in-gel renaturation assays, and western analysis, the activity consists of closely related members of the α branch of the casein kinase 1 family of protein kinases. Because of its tight association with PHFs and its phosphate-directed substrate selectivity, casein kinase 1 is positioned to participate in the pathological hyperphosphorylation of tau protein that is observed in neurodegenerative diseases such as Alzheimer's disease.