Difference between revisions of "Phosphatase Subfamily PPP3C"

Revision as of 17:17, 26 March 2015

Phosphatase Classification: Fold MTDP: Superfamily MTDP: Family PPP: Subfamily PPP3C

PPP3C (PP2B, calcineurin) is a calcium-dependent serine/threonine phosphatase conserved in eukaryotes. It is involved in various biological processes and has significantly clinic relevance.

Evolution

PPP3C is found throughout eukaryotes, including opisthokonta, amoebazoa, plants and etc.

Domain

PPP3C has a single domain - phosphatase domain.

Functions

PPP3C, catalytic subunit of Protein Phosphatase 2B (PP2B) holoenzyme (aka calcineurin). The holoenzyme is heterodimer complex consisting of one catalytic subunit and one regulatory subunit participates in very various cellular processes, from cell cycle progression to cardiac hypertrophy [1]. In particular, it activates the T cells of the immune system in mammals. When an antigen-preseting cell interacts with a T cell receptor on T cells, the cytoplasmic level of calcium increases, which activates calcineurin. Calcineurin activates a vertebrate-specific transcription factor called NFATc. It is used as a target for several immunosuppressive drugs. This phosphatase has clinical significance for schizophrenia and diabetes (see wikipedia). Calcineurin is also the drug target of tacrolimus which is an immunosuppressive drug used mainly after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection.

PP2B/calcineurin modulates potassium channel, perhaps by directly controlling the phosphorylation state of potassium channel in collaboration with PKA [2, 3].

References

1. Rusnak F and Mertz P. Calcineurin: form and function. Physiol Rev. 2000 Oct;80(4):1483-521. DOI:10.1152/physrev.2000.80.4.1483 | PubMed ID:11015619 | HubMed [Rusnak00]
2. Orie NN, Thomas AM, Perrino BA, Tinker A, and Clapp LH. Ca2+/calcineurin regulation of cloned vascular K ATP channels: crosstalk with the protein kinase A pathway. Br J Pharmacol. 2009 Jun;157(4):554-64. DOI:10.1111/j.1476-5381.2009.00221.x | PubMed ID:19422382 | HubMed [Orie09]
3. Brignell JL, Perry MD, Nelson CP, Willets JM, Challiss RA, and Davies NW. Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B. PLoS One. 2015;10(3):e0121285. DOI:10.1371/journal.pone.0121285 | PubMed ID:25793374 | HubMed [Brignell15]