A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Attempt to read property "Count" on bool

Filename: helpers/my_audit_helper.php

Line Number: 3100

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Reduction of protein phosphatase 2A (PP2A) complexity reveals cellular functions and dephosphorylation motifs of the PP2A/B'δ holoenzyme. | LitMetric

Reduction of protein phosphatase 2A (PP2A) complexity reveals cellular functions and dephosphorylation motifs of the PP2A/B'δ holoenzyme.

J Biol Chem

Department of Neuroscience and Pharmacology and Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa 52242. Electronic address:

Published: April 2020

AI Article Synopsis

  • Protein phosphatase 2A (PP2A) is a key enzyme family that regulates cellular processes by dephosphorylating Ser/Thr sites, and its function is influenced by various regulatory subunits.
  • Traditional methods to study PP2A's roles have been limited due to high redundancy and expression levels, prompting researchers to simplify PP2A holoenzyme configurations for better insights.
  • By engineering specific charge-swap variants of scaffolding and regulatory subunits, the study demonstrated that PP2A could regulate key signaling pathways, such as those involving extracellular signal-regulated kinase and protein kinase A, while also identifying substrate dephosphorylation motifs through phosphoproteomics.

Article Abstract

Protein phosphatase 2A (PP2A) is a large enzyme family responsible for most cellular Ser/Thr dephosphorylation events. PP2A substrate specificity, localization, and regulation by second messengers rely on more than a dozen regulatory subunits (including B/R2, B'/R5, and B″/R3), which form the PP2A heterotrimeric holoenzyme by associating with a dimer comprising scaffolding (A) and catalytic (C) subunits. Because of partial redundancy and high endogenous expression of PP2A holoenzymes, traditional approaches of overexpressing, knocking down, or knocking out PP2A regulatory subunits have yielded only limited insights into their biological roles and substrates. To this end, here we sought to reduce the complexity of cellular PP2A holoenzymes. We used tetracycline-inducible expression of pairs of scaffolding and regulatory subunits with complementary charge-reversal substitutions in their interaction interfaces. For each of the three regulatory subunit families, we engineered A/B charge-swap variants that could bind to one another, but not to endogenous A and B subunits. Because endogenous Aα was targeted by a co-induced shRNA, endogenous B subunits were rapidly degraded, resulting in expression of predominantly a single PP2A heterotrimer composed of the A/B charge-swap pair and the endogenous catalytic subunit. Using B'δ/PPP2R5D, we show that PP2A complexity reduction, but not PP2A overexpression, reveals a role of this holoenzyme in suppression of extracellular signal-regulated kinase signaling and protein kinase A substrate dephosphorylation. When combined with global phosphoproteomics, the PP2A/B'δ reduction approach identified consensus dephosphorylation motifs in its substrates and suggested that residues surrounding the phosphorylation site play roles in PP2A substrate specificity.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186168PMC
http://dx.doi.org/10.1074/jbc.RA119.011270DOI Listing

Publication Analysis

Top Keywords

regulatory subunits
12
pp2a
11
protein phosphatase
8
phosphatase pp2a
8
pp2a complexity
8
dephosphorylation motifs
8
pp2a substrate
8
substrate specificity
8
pp2a holoenzymes
8
a/b charge-swap
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!