Effects of progesterone and its reduced metabolites, dihydroprogesterone and tetrahydroprogesterone, on the expression and phosphorylation of glycogen synthase kinase-3 and the microtubule-associated protein Tau in the rat cerebellum

2007 ◽  
Vol 67 (4) ◽  
pp. 510-520 ◽  
Author(s):  
Christian Guerra-Araiza ◽  
Miguel A.R. Amorim ◽  
Ignacio Camacho-Arroyo ◽  
Luis M. Garcia-Segura
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
Rat Cerebellum

scholarly journals The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bɛ at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase

2001 ◽  
Vol 355 (3) ◽  
pp. 609-615 ◽  
Author(s):  
Yvonne L. WOODS ◽  
Philip COHEN ◽  
Walter BECKER ◽  
Ross JAKES ◽  
Michel GOEDERT ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Kinases ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Initiation Factor ◽  
Glycogen Synthase Kinase 3 ◽  
General Role ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
Protein Synthesis Initiation

The substrate specificity of glycogen synthase kinase 3 (GSK3) is unusual in that efficient phosphorylation only occurs if another phosphoserine or phosphothreonine residue is already present four residues C-terminal to the site of GSK3 phosphorylation. One such substrate is the ε-subunit of rat eukaryotic protein-synthesis initiation factor 2B (eIF2Bε), which is inhibited by the GSK3-catalysed phosphorylation of Ser535. There is evidence that GSK3 is only able to phosphorylate eIF2Bε at Ser535 if Ser539 is already phosphorylated by another protein kinase. However, no protein kinases capable of phosphorylating Ser539 have so far been identified. Here we show that Ser539 of eIF2Bε, which is followed by proline, is phosphorylated specifically by two isoforms of dual-specificity tyrosine phosphorylated and regulated kinase (DYRK2 and DYRK1A), but only weakly or not at all by other ‘proline-directed’ protein kinases tested. We also establish that phosphorylation of Ser539 permits GSK3 to phosphorylate Ser535in vitro and that eIF2Bε is highly phosphorylated at Ser539in vivo. The DYRK isoforms also phosphorylate human microtubule-associated protein tau at Thr212in vitro, a residue that is phosphorylated in foetal tau and hyperphosphorylated in filamentous tau from Alzheimer's-disease brain. Phosphorylation of Thr212 primes tau for phosphorylation by GSK3 at Ser208in vitro, suggesting a more general role for DYRK isoforms in priming phosphorylation of GSK3 substrates.

scholarly journals Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau

FEBS Letters ◽  
1992 ◽  
Vol 314 (3) ◽  
pp. 315-321 ◽  
Author(s):  
E.-M. Mandelkow ◽  
G. Drewes ◽  
J. Biernat ◽  
N. Gustke ◽  
J. Van Lint ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau

scholarly journals Glycogen Synthase Kinase-3 Regulates Production of Amyloid-βPeptides and Tau Phosphorylation in Diabetic Rat Brain

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Zhong-Sen Qu ◽  
Liang Li ◽  
Xiao-Jiang Sun ◽  
Yu-Wu Zhao ◽  
Jin Zhang ◽  
...  
Keyword(s):  
Rat Brain ◽  
Glycogen Synthase ◽  
Selective Inhibition ◽  
Neurological Complications ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Diabetic Rat ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
Amyloid Deposits

The pathogenesis of diabetic neurological complications is not fully understood. Diabetes mellitus (DM) and Alzheimer’s disease (AD) are characterized by amyloid deposits. Glycogen synthase kinase-3 (GSK-3) plays an important role in the pathogenesis of AD and DM. Here we tried to investigate the production of amyloid-βpeptides (Aβ) and phosphorylation of microtubule-associated protein tau in DM rats and elucidate the role of GSK-3 and Akt (protein kinase B, PKB) in these processes. Streptozotocin injection-induced DM rats displayed an increased GSK-3 activity, decreased activity and expression of Akt. And Aβ40 and Aβ42 were found overproduced and the microtubule-associated protein tau was hyperphosphorylated in the hippocampus. Furthermore, selective inhibition of GSK-3 by lithium could attenuate the conditions of Aβoverproduction and tau hyperphosphorylation. Taken together, our studies suggest that GSK-3 regulates both the production of Aβand the phosphorylation of tau in rat brain and may therefore contribute to DM caused AD-like neurological defects.

scholarly journals Microtubule-associated protein tau is essential for long-term depression in the hippocampus

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130144 ◽  
Author(s):  
Tetsuya Kimura ◽  
Daniel J. Whitcomb ◽  
Jihoon Jo ◽  
Philip Regan ◽  
Thomas Piers ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Principal Component ◽  
Synaptic Function ◽  
Glycogen Synthase Kinase 3 ◽  
Long Term Depression ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau

The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro , an effect that was replicated by RNAi knockdown of tau in vitro . We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.

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