Calcineurin (PP2B)

Definition
Calcineurin also known as protein phosphatase 2B (PP2B), is a phosphoprotein serine/threonine phosphatase, activated physiologically by Ca2+–calmodulin.

Discovery
It was identified and characterized by Claude Klee and Philip Cohen in the late 1970s.

Structural Characteristics
Calcineurin is a dimer of an A catalytic subunit and a B subunit. Calmodulin becomes tightly associated with calcineurin only in the presence of elevated, but physiological, levels of Ca2+ 1.

Classification
In mammals three isoforms of calcineurin A (Aa, Aß and A?) and two isoforms of calcineurin B (B1, and B2) are expressed from separate genes1.

Mode of action
In resting cells, nuclear factor of activated T-cells (NFAT) proteins are phosphorylated, and in cells exposed to stimuli that raise intracellular free Ca2+ levels, they are dephosphorylated by the calmodulin-dependent phosphatase calcineurin. On dephosphorylation NFAT translocate to the nucleus whereon, it binds to consensus DNA sites and controls gene transcription2.

Functions
Calcineurin plan an important role in intracellular signaling. In budding yeast, calcineurin has a role in coordinating adaptation to environmental stress both through the calcineurin–Crz1p transcriptional pathway and through post-translational mechanisms. Calcineurin signaling is involved in the long-term adaptation after chronic drug treatment in a way that may parallel its role during memory formation3.

References
1.Hogan PG, Li H (2005). Calcineurin. Curr Biol., 15(12):442-443.
2.Valerie Horsley and Grace K. Pavlath (2002). Nfat: ubiquitous regulator of cell differentiation and adaptation. J Cell Biol., 156(5): 771–774.
3.Biala G (2007). Memory processes and addiction: involvement of the calcineurin signaling pathway. Postepy Hig Med Dosw (Online)., 61:199-203.