Dissection of c‐Mpl and Thrombopoietin Function: Studies of Knockout Mice and Receptor Signal Transduction

Stem Cells ◽  
1996 ◽  
Vol 14 (S1) ◽  
pp. 116-123 ◽  
Author(s):  
Austin L. Gurney ◽  
Frederic J. De Sauvage
2021 ◽  
Vol 22 (21) ◽  
pp. 11850
Author(s):  
Han Zhao ◽  
Lingyan Feng ◽  
Wei Zhong ◽  
Hongyan Zhen ◽  
Qingjia Chi ◽  
...  

Melatonin has been indicated to ameliorate tau hyperphosphorylation in the pathogenesis of tau diseases, but the role of melatonin-receptor signal transduction has not been clearly discovered. In this study, we found intensive tau hyperphosphorylation in melatonin receptor knockout mice. Bielschowsky silver staining showed ghostlike neurofibrillary tangles in melatonin receptor-2 knockout (MT2KO) as well as melatonin receptors-1 and -2 knockout (DKO) mice, and an argyrophilic substance was deposited in melatonin receptor-1 knockout (MT1KO) mice. Furthermore, we found significantly decreased activity of protein phosphatase 2A (PP2A) by Western blot and enzyme-linked immunosorbent assay (ELISA), which was partly due to the overexpression of protein phosphatase methylesterase-1 (PME-1), but not glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (CDK5) or protein kinase B (Akt). Finally, we observed a significant increase in cyclic adenosine monophosphate (cAMP) and a decrease in miR-125b-5p levels in MT1KO, MT2KO and DKO mice. Using a luciferase reporter assay, we discovered that miR-125b-5p largely decreased the expression of firefly luciferase by interfering with the 3′UTR of PME-1. Furthermore, miR-125b-5p mimics significantly decreased the expression of PME-1, while miR-125b-5p inhibitor induced tau hyperphosphorylation. These results show that melatonin-receptor signal transduction plays an important role in tau hyperphosphorylation and tangle formation.


1996 ◽  
Vol 71 ◽  
pp. 330
Author(s):  
Kazushi Kushiku ◽  
Ryoko Tokunaga ◽  
Hiromi Yamada ◽  
Kazuhiko Shibata ◽  
Katsuhiro Yamada ◽  
...  

1995 ◽  
Vol 270 (10) ◽  
pp. 5631-5635 ◽  
Author(s):  
Tetsuzo Tauchi ◽  
Gen-Sheng Feng ◽  
Randy Shen ◽  
Maureen Hoatlin ◽  
Grover C. Bagby ◽  
...  

Science ◽  
1991 ◽  
Vol 252 (5014) ◽  
pp. 1839-1842 ◽  
Author(s):  
L. Justement ◽  
K. Campbell ◽  
N. Chien ◽  
J. Cambier

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