Protein phosphatase 2A as therapeutic targets in various disease models

Abstract

There are a large number of signalling pathways responsible for transmitting information within the cell. Although cellular signalling is thought to be majorly governed by protein kinases 'cascade effects'; their antagonists protein phosphatases also play a crucial dual role in signal transduction. By dephosphorylating the proteins involved in signalling pathways, phosphatases may lead to their activation and sometimes they may terminate a signal generated by kinases activity. Due to counterbalancing the function of phosphorylation, the protein phosphatases are very important to signal transduction processes and thus the control of phosphatase activity is as significant as kinases, in the regulation of a plethora of cellular processes. In general, the protein phosphatases are comprised of a catalytic subunit with one or more regulatory and/or targeting subunits associated with it. The Protein Phosphatase 2A (PP2A), a member of serine/threonine phosphatases family, is ubiquitously expressed a remarkably conserved enzyme in the cell. Its catalytic activity has been highly regulated and may have enormous therapeutic potential which is still untapped. It has specificities for a number of substrates which witnessed its involvement in various signalling modules of cell cycle regulation, cell morphology and development. Thus it can be an appropriate target for studying different diseases associated with abnormal signal transduction pathways such as neurodegenerative diseases and malignancies. This review will focus on the structure and regulatory pathways of PP2A. The de-regulation of PP2A in some specific pathology such as Cancer, Heart diseases, Neurodegenerative disorders and Diabetes will also be touched upon.

Keywords: Alzheimer's disease; Cancer; Cell cycle regulation; Cellular signalling; PP2A; Reversible phosphorylation.