Difference between revisions of "Phosphatase Subfamily PPP2C"

Revision as of 20:32, 17 December 2014

Phosphatase Classification: Fold MTDP: Superfamily PPP: Family PPP: Subfamily PPP2C (PP2A)

PPP2C is the catalytic subunit of holoenzyme PP2A. PP2A holoenzymes are heterotrimers consisting of a core dimer of two subunits catalytic subunit (C) and regulatory subunit A (PR65), and a third regulatory subunit B-type [1]. Multiple genes encode each subunits, which resulting in a total of about 75 different holoenzyme compositions [2].

Evolution

PPP2C subfamily is found throughout eukaryotes. Human has two PPP2C: PPP2CA and PPP2CB. In most bilateria, it has a single copy, such as worm, fruit fly and sea urchin. In yeast, it has two copies: PPH21 and PPH22. (Note: the evolution of PP2A holoenzyme should be elucidated.)

Functions

PP2A accounts for the majority of phospho-serine/threonine phosphatase activity in most cells and is involved in the regulation of nearly every cellular process, including different signaling pathways, cell cycle progression, DNA replication, gene transcription and protein translation [3, 4]. It is considered to be a principal guardian against tumorigenic transformation [5]. Some viruses target this protein to hijack the host cell [1].

PPP2C controls the activity of at least 50 different kinases by directly interaction or linked via a anchoring protein. PPP2C not only integrate signals within phoshorylation cascades but also to be the focal point of a distinct post-translational modification, reversible protein methylation [2].

Examples of PP2A functions

Hedgehog signaling

PP2A functions with PPFIA1 to promote the dephosphorylation of Kif7, triggering Kif7 localization to the tips of primary cilia and promoting Gli transcriptional activity. Both Kif7 and Gli are components in Hedgehog signaling [6]. (PS: Interestingly, PPFIA1 is known as interacting partner with tyrosine phosphatase PTPRF.)

References

1. Janssens V, Longin S, and Goris J. PP2A holoenzyme assembly: in cauda venenum (the sting is in the tail). Trends Biochem Sci. 2008 Mar;33(3):113-21. DOI:10.1016/j.tibs.2007.12.004 | PubMed ID:18291659 | HubMed [janssens08]
2. Janssens V, Goris J, and Van Hoof C. PP2A: the expected tumor suppressor. Curr Opin Genet Dev. 2005 Feb;15(1):34-41. DOI:10.1016/j.gde.2004.12.004 | PubMed ID:15661531 | HubMed [janssens05]
3. Janssens V and Goris J. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J. 2001 Feb 1;353(Pt 3):417-39. DOI:10.1042/0264-6021:3530417 | PubMed ID:11171037 | HubMed [janssens01]
4. Sontag E. Protein phosphatase 2A: the Trojan Horse of cellular signaling. Cell Signal. 2001 Jan;13(1):7-16. DOI:10.1016/s0898-6568(00)00123-6 | PubMed ID:11257442 | HubMed [sontag01]
5. Westermarck J and Hahn WC. Multiple pathways regulated by the tumor suppressor PP2A in transformation. Trends Mol Med. 2008 Apr;14(4):152-60. DOI:10.1016/j.molmed.2008.02.001 | PubMed ID:18329957 | HubMed [westermarck08]
6. Liu YC, Couzens AL, Deshwar AR, B McBroom-Cerajewski LD, Zhang X, Puviindran V, Scott IC, Gingras AC, Hui CC, and Angers S. The PPFIA1-PP2A protein complex promotes trafficking of Kif7 to the ciliary tip and Hedgehog signaling. Sci Signal. 2014 Dec 9;7(355):ra117. DOI:10.1126/scisignal.2005608 | PubMed ID:25492966 | HubMed [liu14]