scholarly journals Microcystin-Leucine-Arginine Induces Tau Pathology Through Bα Degradation via Protein Phosphatase 2A Demethylation and Associated Glycogen Synthase Kinase-3β Phosphorylation

2018 ◽  
Vol 162 (2) ◽  
pp. 475-487 ◽  
Author(s):  
Yali Zhang ◽  
Jiahui Zhang ◽  
Enhao Wang ◽  
Wei Qian ◽  
Yan Fan ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Glycogen Synthase ◽  
Protein Phosphatase 2A ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Tau Pathology ◽  
Phosphatase 2A

scholarly journals Glycogen synthase kinase-3β regulates leucine-309 demethylation of protein phosphatase-2A via PPMT1 and PME-1

FEBS Letters ◽  
2012 ◽  
Vol 586 (16) ◽  
pp. 2522-2528 ◽  
Author(s):  
Xiu-Qing Yao ◽  
Xia-Chun Li ◽  
Xiao-Xue Zhang ◽  
Yang-Yang Yin ◽  
Bin Liu ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Glycogen Synthase ◽  
Protein Phosphatase 2A ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Phosphatase 2A

Glycogen synthase kinase-3β regulates Tyr307 phosphorylation of protein phosphatase-2A via protein tyrosine phosphatase 1B but not Src

2011 ◽  
Vol 437 (2) ◽  
pp. 335-344 ◽  
Author(s):  
Xiu-Qing Yao ◽  
Xiao-Xue Zhang ◽  
Yang-Yang Yin ◽  
Bin Liu ◽  
Dan-Ju Luo ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Protein Phosphatase ◽  
Glycogen Synthase ◽  
Protein Phosphatase 2A ◽  
Tyrosine Phosphatase ◽  
Glycogen Synthase Kinase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Glycogen Synthase Kinase 3Β ◽  
Phosphatase 2A ◽  
Gsk 3Β

GSK-3β (glycogen synthase kinase-3β), a crucial tau kinase, negatively regulates PP2A (protein phosphatase 2A), the most active tau phosphatase that is suppressed in the brain in AD (Alzheimer's disease). However, the molecular mechanism is not understood. In the present study we found that activation of GSK-3β stimulates the inhibitory phosphorylation of PP2A at Tyr307 (pY307-PP2A), whereas inhibition of GSK-3β decreased the level of pY307-PP2A both in vitro and in vivo. GSK-3β is a serine/threonine kinase that can not phosphorylate tyrosine directly, therefore we measured PTP1B (protein tyrosine phosphatase 1B) and Src (a tyrosine kinase) activities. We found that GSK-3β can modulate both PTP1B and Src protein levels, but it only inhibits PTP1B activity, with no effect on Src. Furthermore, only knockdown of PTP1B but not Src by siRNA (small interfering RNA) eliminates the effects of GSK-3β on PP2A. GSK-3β phosphorylates PTP1B at serine residues, and activation of GSK-3β reduces the mRNA level of PTP1B. Additionally, we also observed that GSK-3 negatively regulates the protein and mRNA levels of PP2A, and knockdown of CREB (cAMP-response-element-binding protein) abolishes the increase in PP2A induced by GSK-3 inhibition. The results of the present study suggest that GSK-3β inhibits PP2A by increasing the inhibitory Tyr307 phosphorylation and decreasing the expression of PP2A, and the mechanism involves inhibition of PTP1B and CREB.

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