Protein Serine/Threonine Phosphatases: Keys to Unlocking Regulators and Substrates.


Journal Article (Review)

Protein serine/threonine phosphatases (PPPs) are ancient enzymes, with distinct types conserved across eukaryotic evolution. PPPs are segregated into types primarily on the basis of the unique interactions of PPP catalytic subunits with regulatory proteins. The resulting holoenzymes dock substrates distal to the active site to enhance specificity. This review focuses on the subunit and substrate interactions for PPP that depend on short linear motifs. Insights about these motifs from structures of holoenzymes open new opportunities for computational biology approaches to elucidate PPP networks. There is an expanding knowledge base of posttranslational modifications of PPP catalytic and regulatory subunits, as well as of their substrates, including phosphorylation, acetylation, and ubiquitination. Cross talk between these posttranslational modifications creates PPP-based signaling. Knowledge of PPP complexes, signaling clusters, as well as how PPPs communicate with each other in response to cellular signals should unlock the doors to PPP networks and signaling "clouds" that orchestrate and coordinate different aspects of cell physiology.

Full Text

Duke Authors

Cited Authors

  • Brautigan, DL; Shenolikar, S

Published Date

  • June 20, 2018

Published In

Volume / Issue

  • 87 /

Start / End Page

  • 921 - 964

PubMed ID

  • 29925267

Pubmed Central ID

  • 29925267

Electronic International Standard Serial Number (EISSN)

  • 1545-4509

Digital Object Identifier (DOI)

  • 10.1146/annurev-biochem-062917-012332


  • eng

Conference Location

  • United States