title: Kinase-kinase interaction and modulation of tau phosphorylation.
abstract: The microtubule (MT)-associated protein tau attaches to neuronal MT networks and regulates their integrity. The phosphorylation state of tau alters its binding activity. MT integrity is maintained by the phosphorylation state of tau, which is under the control of the kinase-phosphatase balance. This control requires the proper regulation of topographical and temporal characteristics of tau kinases and phosphatases. The tau phosphorylation protein complex (TPPC) anchors tau kinases and phosphatases via scaffold proteins, tau effectors, and tau itself. Targeting these proteins in TPPC fulfills the topographical requirements for maintaining MT functions. The switching of tau kinase activity determines the order of the kinase action. The combined action of kinases is temporally modulated; reversal of the time order of events results in a differential state of tau phosphorylation. Elucidation of protein-protein interaction in the regulation of tau phosphorylation will shed light on the physiology and pathology of tau phosphorylation.
authors.affiliation: Department of Physiology, Tokyo Medical University, Shinjuku, Tokyo, Japan. m-hasigu@tokyo-med.ac.jp
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Hashiguchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Hashiguchi
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000737:chemistry / Q000378:metabolism*; D048909:Diabetes Complications / Q000209:etiology / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; C054369:MAPT protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; D017868:Cyclic AMP-Dependent Protein Kinases; C079134:tau protein kinase II; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase