Tau and GSK3beta dephosphorylations are required for regulating Pin1 phosphorylation.
Pin1 binds mitotically phosphorylated Thr231-Pro232 and Thr212-Pro213 sites on tau, and a Pin1 deficiency in mice leads to tau hyperphosphorylation. The aim of this study was to determine if the dephosphorylation or inhibition of tau and GSK3beta phosphorylation induces the Pin1 phosphorylation. To test this, human SK-N-MC cells were stably transfected with a fusion gene containing neuron-specific enolase (NSE)-controlled APPsw gene(NSE/APPsw), to induce Abeta-42. The stable transfectants were then transiently transfected with NSE/Splice, lacking human tau (NSE/Splice), or NSE/hTau, containing human tau, into the cells. The NSE/Splice- and NSE/hTau-cells were then treated with lithium. We concluded that (i) there was more C99-beta APP accumulation than C83-betaAPP in APPsw-tansfectant and thereby promoted Abeta-42 production in transfectants. (ii) the inhibition of tau and GSK3beta phosphorylations correlated with increase in Pin1 activation in NSE/hTau- cells. Thus, these observations suggest that Pin1 might have an inhibitive role in phosphorylating tau and GSK3beta for protecting against Alzheimer's disease.
Min
Sae H
SH
Division of Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA, 122-704, Seoul, Korea.
Cho
Jung S
JS
Oh
Jae H
JH
Shim
Sun B
SB
Hwang
Dae Y
DY
Lee
Su H
SH
Jee
Seung W
SW
Lim
Hwa J
HJ
Kim
Min Y
MY
Sheen
Yhun Y
YY
Lee
Seok H
SH
Kim
Yong K
YK
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017931:DNA Primers; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D016875:tau Proteins / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D017931:DNA Primers; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse