scholarly journals Nck in a Complex Containing the Catalytic Subunit of Protein Phosphatase 1 Regulates Eukaryotic Initiation Factor 2α Signaling and Cell Survival to Endoplasmic Reticulum Stress

2006 ◽  
Vol 281 (36) ◽  
pp. 26633-26644 ◽  
Author(s):  
Mathieu Latreille ◽  
Louise Larose
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Survival ◽  
Protein Phosphatase ◽  
Catalytic Subunit ◽  
Protein Phosphatase 1 ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor

scholarly journals High Glucose Exposure Promotes Activation of Protein Phosphatase 2A in Rodent Islets and INS-1 832/13 β-Cells by Increasing the Posttranslational Carboxylmethylation of Its Catalytic Subunit

Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 380-391 ◽  
Author(s):  
Daleep K. Arora ◽  
Baker Machhadieh ◽  
Andrea Matti ◽  
Brian E. Wadzinski ◽  
Sasanka Ramanadham ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Hormone Secretion ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Cellular Functions ◽  
Phosphatase 2A ◽  
Normal Rat

Existing evidence implicates regulatory roles for protein phosphatase 2A (PP2A) in a variety of cellular functions, including cytoskeletal remodeling, hormone secretion, and apoptosis. We report here activation of PP2A in normal rat islets and insulin-secreting INS-1 832/13 cells under the duress of hyperglycemic (HG) conditions. Small interfering RNA-mediated knockdown of the catalytic subunit of PP2A (PP2Ac) markedly attenuated glucose-induced activation of PP2A. HG, but not nonmetabolizable 3-O-methyl glucose or mannitol (osmotic control), significantly stimulated the methylation of PP2Ac at its C-terminal Leu-309, suggesting a novel role for this posttranslational modification in glucose-induced activation of PP2A. Moreover, knockdown of the cytosolic leucine carboxymethyl transferase 1 (LCMT1), which carboxymethylates PP2Ac, significantly attenuated PP2A activation under HG conditions. In addition, HG conditions, but not 3-O-methyl glucose or mannitol, markedly increased the expression of LCMT1. Furthermore, HG conditions significantly increased the expression of B55α, a regulatory subunit of PP2A, which has been implicated in islet dysfunction under conditions of oxidative stress and diabetes. Thapsigargin, a known inducer of endoplasmic reticulum stress, failed to exert any discernible effects on the carboxymethylation of PP2Ac, expression of LCMT1 and B55α, or PP2A activity, suggesting no clear role for endoplasmic reticulum stress in HG-induced activation of PP2A. Based on these findings, we conclude that exposure of the islet β-cell to HG leads to accelerated PP2A signaling pathway, leading to loss in glucose-induced insulin secretion.

scholarly journals The MyD116 African Swine Fever Virus Homologue Interacts with the Catalytic Subunit of Protein Phosphatase 1 and Activates Its Phosphatase Activity

2007 ◽  
Vol 81 (6) ◽  
pp. 2923-2929 ◽  
Author(s):  
José Rivera ◽  
Charles Abrams ◽  
Bruno Hernáez ◽  
Alberto Alcázar ◽  
José M. Escribano ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Catalytic Subunit ◽  
Protein Phosphatase 1 ◽  
Initiation Factor ◽  
Wild Type ◽  
Α Subunit ◽  
Initiation Factor 2

ABSTRACT The DP71L protein of African swine fever virus (ASFV) shares sequence similarity with the herpes simplex virus ICP34.5 protein over a C-terminal domain. We showed that the catalytic subunit of protein phosphatase 1 (PP1) interacts specifically with the ASFV DP71L protein in a yeast two-hybrid screen. The chimeric full-length DP71L protein, from ASFV strain Badajoz 71 (BA71V), fused to glutathione S-transferase (DP71L-GST) was expressed in Escherichia coli and shown to bind specifically to the PP1-α catalytic subunit expressed as a histidine fusion protein (6×His-PP1α) in E. coli. The functional effects of this interaction were investigated by measuring the levels of PP1 and PP2A in ASFV-infected Vero cells. This showed that infection with wild-type ASFV strain BA71V activated PP1 between two- and threefold over that of mock-infected cells. This activation did not occur in cells infected with the BA71V isolate in which the DP71L gene had been deleted, suggesting that expression of DP71L leads to PP1 activation. In contrast, no effect was observed on the activity of PP2A following ASFV infection. We showed that infection of cells with wild-type BA71V virus resulted in decreased phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF-2α). ICP34.5 recruits PP1 to dephosphorylate the α subunit of eukaryotic translational initiation factor 2 (also known as eIF-2α); possibly the ASFV DP71L protein has a similar function.

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