Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling

Protein phosphatase 2A (PP2A) comprises a family of serine/threonine phosph atases, minimally containing a well conserved catalytic subunit, the activi ty of which is highly regulated. Regulation is accomplished mainly by membe rs of a family of regulatory subunits, which determine the substrate specif icity. (sub)cellular localization and catalytic activity of the PP2A holoen zymes. Moreover, the catalytic subunit is subject to two types of post-tran slational modification, phosphorylation and methylation, which are also tho ught to be important regulatory devices, The regulatory ability of PTPA (PT Pase activator), originally identified as a protein stimulating the phospho tyrosine phosphatase activity of PP2A, will also be discussed, alongside th e other regulatory inputs. The use of specific PP2A inhibitors and molecula r genetics in yeast, Drosophila and mice has revealed roles for PP2A in cel l cycle regulation, cell morphology and development, PP2A also plays a prom inent role in the regulation of specific signal transduction cascades, as w itnessed by its presence in a number of macromolecular signalling modules, where it is often found in association with other phosphatases and kinases. Additionally, PP2A interacts with a substantial number of other cellular a nd viral proteins. which are PP2A substrates, target PP2A to different subc ellular compartments or affect enzyme activity. Finally, the de-regulation of PP2A in some specific pathologies will be touched upon.