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Casein Kinase 1 Is Tightly Associated with Paired‐Helical Filaments Isolated from Alzheimer's Disease Brain
Author(s) -
Kuret Jeff,
Johnson Ginger S.,
Cha Donald,
Christenson Erik R.,
DeMaggio Anthony J.,
Hoekstra Merl F.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69062506.x
Subject(s) - casein kinase 1 , casein , casein kinase 2 , kinase , hyperphosphorylation , alzheimer's disease , chemistry , biochemistry , casein kinase 2, alpha 1 , protein kinase a , substrate (aquarium) , selectivity , biology , mitogen activated protein kinase kinase , medicine , disease , ecology , catalysis
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.