Calcineurin
Template:PBB Protein phosphatase 3 (formerly 2B), catalytic subunit, alpha isoform, also known as PPP3CA, is a human gene.[1]
Calcineurin (CN) is a protein phosphatase also known as protein phosphatase 2B (PP2B). Calcineurin is responsible for activating the transcription of interleukin 2 (IL-2), that stimulates the growth and differentiation of T cell response. In immunosuppressive therapy it is inhibited by cyclosporin, pimecrolimus (Elidel) and tacrolimus (FK506) - these drugs are known as calcineurin inhibitors. Calcineurin dephosphorylates Nuclear factor of activated T cell, cytoplasmic component (NFATc), a transcription factor that can then go into the nucleus and turn on genes involved in IL-2 synthesis.
Mechanism of action
When an antigen presenting cell interacts with a T cell receptor on T cells, there is an increase in the cytoplasmic level of calcium, which [2] activates calcineurin, by binding a regulatory subunit and activating calmodulin binding. Calcineurin induces different transcription factors (NF-ATs) that are important in the transcription of IL-2 genes. IL-2 activates T-helper lymphocytes and induces the production of other cytokines. In this way, it governs the action of cytotoxic lymphocytes and NK cells. The amount of IL-2 being produced by the T-helper cells is believed to influence the extent of the immune response significantly.
Research into Schizophrenia
Calcineurin is linked to receptors for two brain chemicals, NMDA and dopamine. An MIT experiment with genetically-altered mice that could not produce calcineurin showed similar symptoms as in humans with schizophrenia: impairment in working memory, attention deficits, aberrant social behavior and several other abnormalities characteristic of schizophrenia.[3]
Research into Diabetes
Scientist believe that calcineurin might prove to be one of the two keys, along with NFAT, in improving the function of diabetics' pancreatic beta cells.[4][5]
Calcineurin/Nfat signaling is required for perinatal lung maturation and function:[6]
References
- ^ "Entrez Gene: PPP3CA protein phosphatase 3 (formerly 2B), catalytic subunit, alpha isoform".
- ^ T Cell Receptor–Induced Calcineurin Activation Regulates T Helper Type 2 Cell Development by Modifying the Interleukin 4 Receptor Signaling Complex
- ^ MIT research may lead to better schizophrenia drugs - MIT News Office
- ^ BBC NEWS | Health | Hope for new diabetes treatment
- ^ Hope for significant new diabetes treatment in Stanford discovery
- ^ Calcineurin helps newborns breathe easy
Further reading
External links
- Calcineurin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Template:EMedicineDictionary
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