PP2A-B55: substrates and regulators in the control of cellular functions

PP2A is a major serine/threonine phosphatase class involved in the regulation of cell signaling through the removal of protein phosphorylation. This class of phosphatases is comprised of different heterotrimeric complexes displaying distinct substrate specificities. The present review will focus on one specific heterocomplex, the phosphatase PP2A-B55. Herein, we will report the direct substrates of this phosphatase identified to date, and its impact on different cell signaling cascades. We will additionally describe its negative regulation by its inhibitors Arpp19 and ENSA and their upstream kinase Greatwall. Finally, we will describe the essential molecular features defining PP2A-B55 substrate specificity that confer the correct temporal pattern of substrate dephosphorylation. The main objective of this review is to provide the reader with a unique source compiling all the knowledge of this particular holoenzyme that has evolved as a key enzyme for cell homeostasis and cancer development.

Automated summary

PP2A is a major serine/threonine phosphatase involved in cell signaling regulation, with different complexes like PP2A-B55 having specific substrate specificity and being negatively regulated by inhibitors and upstream kinases, defining temporal patterns of substrate dephosphorylation. This review aims to compile all knowledge of PP2A-B55, a key enzyme in cell homeostasis and cancer development.