scholarly journals Protein Phosphatase 2A Reactivates FOXO3a through a Dynamic Interplay with 14-3-3 and AKT

2010 ◽  
Vol 21 (6) ◽  
pp. 1140-1152 ◽  
Author(s):  
Amrik Singh ◽  
Min Ye ◽  
Octavian Bucur ◽  
Shudong Zhu ◽  
Maria Tanya Santos ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Transcriptional Activation ◽  
Protein Phosphatase ◽  
Nuclear Translocation ◽  
Akt Phosphorylation ◽  
Forkhead Box ◽  
Phosphatase 2A ◽  
And Function ◽  
Dynamic Interplay

Forkhead box transcription factor FOXO3a, a key regulator of cell survival, is regulated by reversible phosphorylation and subcellular localization. Although the kinases regulating FOXO3a activity have been characterized, the role of protein phosphatases (PP) in the control of FOXO3a subcellular localization and function is unknown. In this study, we detected a robust interaction between FOXO3a and PP2A. We further demonstrate that 14-3-3, while not impeding the interaction between PP2A and FOXO3a, restrains its activity toward AKT phosphorylation sites T32/S253. Disruption of PP2A function revealed that after AKT inhibition, PP2A-mediated dephosphorylation of T32/S253 is required for dissociation of 14-3-3, nuclear translocation, and transcriptional activation of FOXO3a. Our findings reveal that distinct phosphatases dephosphorylate conserved AKT motifs within the FOXO family and that PP2A is entwined in a dynamic interplay with AKT and 14-3-3 to directly regulate FOXO3a subcellular localization and transcriptional activation.

scholarly journals Role of Protein Phosphatase 2A in Osteoblast Differentiation and Function

2017 ◽  
Vol 6 (3) ◽  
pp. 23 ◽  
Author(s):  
Hirohiko Okamura ◽  
Kaya Yoshida ◽  
Hiroyuki Morimoto ◽  
Jumpei Teramachi ◽  
Kazuhiko Ochiai ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Osteoblast Differentiation ◽  
Protein Phosphatase 2A ◽  
Phosphatase 2A ◽  
And Function

2214 Role of protein phosphatase 2A in hippocampal long-term potentiation

1997 ◽  
Vol 28 ◽  
pp. S254
Author(s):  
Kohji Fukunaga ◽  
Dominique Muller ◽  
Masao Ohmitsu ◽  
Eishichi Miyamoto
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Phosphatase 2A

scholarly journals Role of Protein Phosphatase 2A in Regulating the Visual Signaling in Drosophila

2008 ◽  
Vol 28 (6) ◽  
pp. 1444-1451 ◽  
Author(s):  
N. Wang ◽  
H.-T. Leung ◽  
W. L. Pak ◽  
Y. T. Carl ◽  
B. E. Wadzinski ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Visual Signaling ◽  
Phosphatase 2A

scholarly journals The Ser/Thr kinase p90RSK promotes kidney fibrosis by modulating fibroblast–epithelial crosstalk

2019 ◽  
Vol 294 (25) ◽  
pp. 9901-9910 ◽  
Author(s):  
Ling Lin ◽  
Chaowen Shi ◽  
Zhaorui Sun ◽  
Nhat-Tu Le ◽  
Jun-Ichi Abe ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Nuclear Translocation ◽  
Disease Model ◽  
Kidney Fibrosis ◽  
Cellular Processes ◽  
Ribosomal Protein S6 ◽  
Forkhead Box

Healthy kidney structure and environment rely on epithelial integrity and interactions between epithelial cells and other kidney cells. The Ser/Thr kinase 90 kDa ribosomal protein S6 kinase 1 (p90RSK) belongs to a protein family that regulates many cellular processes, including cell motility and survival. p90RSK is predominantly expressed in the kidney, but its possible role in chronic kidney disease (CKD) remains largely unknown. Here, we found that p90RSK expression is dramatically activated in a classic mouse obstructive chronic kidney disease model, largely in the interstitial FSP-1–positive fibroblasts. We generated FSP-1–specific p90RSK transgenic mouse (RSK-Tg) and discovered that these mice, after obstructive injury, display significantly increased fibrosis and enhanced tubular epithelial damage compared with their wt littermates (RSK-wt), indicating a role of p90RSK in fibroblast–epithelial communication. We established an in vitro fibroblast–epithelial coculture system with primary kidney fibroblasts from RSK-Tg and RSK-wt mice and found that RSK-Tg fibroblasts consistently produce excessive H2O2 causing epithelial oxidative stress and inducing nuclear translocation of the signaling protein β-catenin. Epithelial accumulation of β-catenin, in turn, promoted epithelial apoptosis by activating the transcription factor forkhead box class O1 (FOXO1). Of note, blockade of reactive oxygen species (ROS) or β-catenin or FOXO1 activity abolished fibroblast p90RSK-mediated epithelial apoptosis. These results make it clear that p90RSK promotes kidney fibrosis by inducing fibroblast-mediated epithelial apoptosis through ROS-mediated activation of β-catenin/FOXO1 signaling pathway.

Critical role of the N-terminal cyclic AMP-binding domain of Epac2 in its subcellular localization and function

2009 ◽  
Vol 219 (3) ◽  
pp. 652-658 ◽  
Author(s):  
Manabu Niimura ◽  
Takashi Miki ◽  
Tadao Shibasaki ◽  
Wakako Fujimoto ◽  
Toshihiko Iwanaga ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Subcellular Localization ◽  
Critical Role ◽  
Binding Domain ◽  
And Function

scholarly journals Parathyroid Hormone-Related Peptide Represses Chondrocyte Hypertrophy through a Protein Phosphatase 2A/Histone Deacetylase 4/MEF2 Pathway

2009 ◽  
Vol 29 (21) ◽  
pp. 5751-5762 ◽  
Author(s):  
Elena Kozhemyakina ◽  
Todd Cohen ◽  
Tso-Pang Yao ◽  
Andrew B. Lassar
Keyword(s):  
Parathyroid Hormone ◽  
Histone Deacetylase ◽  
Protein Phosphatase ◽  
Transcriptional Activity ◽  
Nuclear Translocation ◽  
Chondrocyte Hypertrophy ◽  
Related Peptide ◽  
Phosphatase 2A ◽  
Histone Deacetylase 4 ◽  
Parathyroid Hormone Related Peptide

ABSTRACT The maturation of immature chondrocytes to hypertrophic chondrocytes is regulated by parathyroid hormone-related peptide (PTHrP). We demonstrate that PTHrP or forskolin administration can block induction of collagen X-luciferase by exogenous Runx2, MEF2, and Smad1 in transfected chondrocytes. We have found that PTHrP/forskolin administration represses the transcriptional activity of MEF2 and that forced expression of MEF2-VP16 can restore expression of the collagen X reporter in chondrocytes treated with these agents. PTHrP/forskolin induces dephosphorylation of histone deacetylase 4 (HDAC4) phospho-S246, which decreases interaction of HDAC4 with cytoplasmic 14-3-3 proteins and promotes nuclear translocation of HDAC4 and repression of MEF2 transcriptional activity. We have found that forskolin increases the activity of an HDAC4 phospho-S246 phosphatase and that forskolin-induced nuclear translocation of HDAC4 was reversed by the protein phosphatase 2A (PP2A) antagonist, okadaic acid. Finally, we demonstrate that knockdown of PP2A inhibits forskolin-induced nuclear translocation of HDAC4 and attenuates the ability of this signaling molecule to repress collagen X expression in chondrocytes, indicating that PP2A is critical for PTHrP-mediated regulation of chondrocyte hypertrophy.

scholarly journals Role of Protein Phosphatase 2A in mGluR5-regulated MEK/ERK Phosphorylation in Neurons

2005 ◽  
Vol 280 (13) ◽  
pp. 12602-12610 ◽  
Author(s):  
Limin Mao ◽  
Lu Yang ◽  
Anish Arora ◽  
Eun Sang Choe ◽  
Guochi Zhang ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Erk Phosphorylation ◽  
Phosphatase 2A
Sign in / Sign up

Export Citation Format

Share Document