Dephosphorylation of microtubule-associated protein tau by protein phosphatase 5.
Protein phosphatase 5 (PP5) is a 58-kDa novel phosphoseryl/phosphothreonyl protein phosphatase. It is ubiquitously expressed in all mammalian tissues examined, with a high level in the brain, but little is known about its physiological substrates. We found that this phosphatase dephosphorylated recombinant tau phosphorylated with cAMP-dependent protein kinase and glycogen synthase kinase-3beta, as well as abnormally hyperphosphorylated tau isolated from brains of patients with Alzheimer's disease. The specific activity of PP5 toward tau was comparable to those reported with other protein substrates examined to date. The PP5 activity toward tau was stimulated by arachidonic acid by 30- to 45-fold. Immunostaining demonstrated that PP5 was primarily cytoplasmic in PC12 cells and in neurons of postmortem human brain tissue. A small pool of PP5 associated with microtubules. Expression of active PP5 in PC12 cells resulted in reduced phosphorylation of tau, suggesting that PP5 can also dephosphorylate tau in cells. These results suggest that PP5 plays a role in the dephosphorylation of tau and might be involved in the molecular pathogenesis of Alzheimer's disease.
Gong
Cheng-Xin
CX
New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA. cgong@ultinet.net
Liu
Fei
F
Wu
Guoxin
G
Rossie
Sandra
S
Wegiel
Jerzy
J
Li
Liang
L
Grundke-Iqbal
Inge
I
Iqbal
Khalid
K
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D016875:tau Proteins / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D016875:tau Proteins; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5