Transglutaminase-2 induces N-cadherin expression in TGF-β1-induced epithelial mesenchymal transition via c-Jun-N-terminal kinase activation by protein phosphatase 2A down-regulation

2013 ◽  
Vol 49 (7) ◽  
pp. 1692-1705 ◽  
Author(s):  
Mi Kyung Park ◽  
Hye Jin You ◽  
He Ja Lee ◽  
Ju Hee Kang ◽  
Seung Hyun Oh ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Epithelial Mesenchymal Transition ◽  
Protein Phosphatase 2A ◽  
Transglutaminase 2 ◽  
Down Regulation ◽  
Kinase Activation ◽  
Mesenchymal Transition ◽  
Phosphatase 2A ◽  
Tgf Β1

scholarly journals Cardamonin Suppresses TGF-β1-Induced Epithelial Mesenchymal Transition via Restoring Protein Phosphatase 2A Expression

2015 ◽  
Vol 23 (2) ◽  
pp. 141-148 ◽  
Author(s):  
Eun Ji Kim ◽  
Hyun Ji Kim ◽  
Mi Kyung Park ◽  
Gyeung Jin Kang ◽  
Hyun Jung Byun ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Epithelial Mesenchymal Transition ◽  
Protein Phosphatase 2A ◽  
Mesenchymal Transition ◽  
Phosphatase 2A ◽  
Tgf Β1

scholarly journals Raf-1-associated Protein Phosphatase 2A as a Positive Regulator of Kinase Activation

2000 ◽  
Vol 275 (29) ◽  
pp. 22300-22304 ◽  
Author(s):  
Dietmar Abraham ◽  
Klaus Podar ◽  
Margit Pacher ◽  
Markus Kubicek ◽  
Natascha Welzel ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Kinase Activation ◽  
Positive Regulator ◽  
Phosphatase 2A

scholarly journals Leucine Carboxyl Methyltransferase 1 (LCMT1)-dependent Methylation Regulates the Association of Protein Phosphatase 2A and Tau Protein with Plasma Membrane Microdomains in Neuroblastoma Cells

2013 ◽  
Vol 288 (38) ◽  
pp. 27396-27405 ◽  
Author(s):  
Jean-Marie Sontag ◽  
Viyada Nunbhakdi-Craig ◽  
Estelle Sontag
Keyword(s):  
Plasma Membrane ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Membrane Microdomains ◽  
Phosphorylated Tau ◽  
Down Regulation ◽  
N2a Cells ◽  
Carboxyl Methyltransferase ◽  
Phosphatase 2A ◽  
Plasma Membrane Microdomains

Down-regulation of protein phosphatase 2A (PP2A) methylation occurs in Alzheimer disease (AD). However, the regulation of PP2A methylation remains poorly understood. We have reported that altered leucine carboxyl methyltransferase (LCMT1)-dependent PP2A methylation is associated with down-regulation of PP2A holoenzymes containing the Bα subunit (PP2A/Bα) and subsequent accumulation of phosphorylated Tau in N2a cells, in vivo and in AD. Here, we show that pools of LCMT1, methylated PP2A, and PP2A/Bα are co-enriched in cholesterol-rich plasma membrane microdomains/rafts purified from N2a cells. In contrast, demethylated PP2A is preferentially distributed in non-rafts wherein small amounts of the PP2A methylesterase PME-1 are exclusively present. A methylation-incompetent PP2A mutant is excluded from rafts. Enhanced methylation of PP2A promotes the association of PP2A and Tau with the plasma membrane. Altered PP2A methylation following expression of a catalytically inactive LCMT1 mutant, knockdown of LCMT1, or alterations in one-carbon metabolism all result in a loss of plasma membrane-associated PP2A and Tau in N2a cells. This correlates with accumulation of soluble phosphorylated Tau, a hallmark of AD and other tauopathies. Thus, our findings reveal a distinct compartmentalization of PP2A and PP2A regulatory enzymes in plasma membrane microdomains and identify a novel methylation-dependent mechanism involved in modulating the targeting of PP2A, and its substrate Tau, to the plasma membrane. We propose that alterations in the membrane localization of PP2A and Tau following down-regulation of LCMT1 may lead to PP2A and Tau dysfunction in AD.

scholarly journals LRG1 promotes epithelial-mesenchymal transition of retinal pigment epithelium cells by activating NOX4

2021 ◽  
Vol 14 (3) ◽  
pp. 349-355
Author(s):  
Li Zhou ◽  
◽  
Wen-Juan Chu ◽  
Ling-Ling Yang ◽  
Hai-Feng Xu ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Protein Expression ◽  
Epithelial Mesenchymal Transition ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Down Regulation ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Mrna And Protein Expression ◽  
Tgf Β1

AIM: To investigate the effect of leucine-rich-alpha-2-glycoprotein 1 (LRG1) on epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE) cells, and to explore the role of NADPH oxidase 4 (NOX4). METHODS: RPE cells (ARPE-19 cell line) were treated with transforming growth factor-β1 (TGF-β1) to induce EMT. Changes of the mRNA and protein expression levels of LRG1 were tested in the TGF-β1 treated cells. The recombinant human LRG1 protein (rLRG1) and siRNA of LRG1 were used to establish accumulation of exogenous LRG1 model and the down-regulation of LRG1 model in ARPE-19 cells respectively, and to detect EMT-related markers including fibronectin, α-smooth muscle actin (α-SMA) and zonula occludens-1 (ZO-1). The mRNA and protein expression level of NOX4 were measured according to the above treatments. VAS2870 was used as a NOX4 inhibitor in rLRG1-treated cells. EMT-related markers were detected to verify the effect of NOX4 in the process of EMT. RESULTS: TGF-β1 promoted the expression of LRG1 at both the mRNA and protein levels during the process of EMT which showed the up-regulation of fibronectin and α-SMA, as well as the down-regulation of ZO-1. Furthermore, the rLRG1 promoted EMT of ARPE-19 cells, which manifested high levels of fibronectin and α-SMA and low level of ZO-1, whereas knockdown of LRG1 prevented EMT by decreasing the expressions of fibronectin and α-SMA and increasing the expression of ZO-1 in ARPE-19 cells. Besides, the rLRG1 activated and LRG1 siRNA suppressed NOX4 expression. EMT was inhibited when VAS2870 was used in the rLRG1-treated cells. CONCLUSION: These results for the first time demonstrate that LRG1 promotes EMT of RPE cells by activating NOX4, which may provide a novel direction to explore the mechanisms of subretinal fibrosis.

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