Calcineurin
Encyclopedia
Calcineurin is a protein phosphatase also known as protein
phosphatase
3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B (PP2B). It activates the T cells of the immune system and can be blocked by drugs. Calcineurin activates NFATc
(Nuclear Factor of Activated T cell, cytoplasmic), a transcription factor
, by dephosphorylating
it. The activated NFATc is then translocated into the nucleus, where it upregulates the expression of interleukin 2
(IL-2), which, in turn, stimulates the growth and differentiation of T cell response. Calcineurin is the target of a class of drugs called calcineurin inhibitors, which includes cyclosporine, pimecrolimus
and tacrolimus
.
interacts with a T cell receptor
on T cell
s, there is an increase in the cytoplasmic level of calcium, which activates calcineurin, by binding a regulatory subunit and activating calmodulin
binding. Calcineurin induces different transcription factors (NFAT
s) 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 lymphocyte
s 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.
, dopamine
and GABA
. An 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.
beta cells.
Calcineurin/Nfat signaling is required for perinatal lung maturation and function.
with DSCR1
and AKAP5
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
phosphatase
Phosphatase
A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...
3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B (PP2B). It activates the T cells of the immune system and can be blocked by drugs. Calcineurin activates NFATc
NFATC1
Nuclear factor of activated T-cells, cytoplasmic 1 is a protein that in humans is encoded by the NFATC1 gene.-Further reading:- External links :...
(Nuclear Factor of Activated T cell, cytoplasmic), a transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
, by dephosphorylating
Dephosphorylation
Dephosphorylation is the essential process of removing phosphate groups from an organic compound by hydrolysis. Its opposite is phosphorylation...
it. The activated NFATc is then translocated into the nucleus, where it upregulates the expression of interleukin 2
Interleukin 2
Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
(IL-2), which, in turn, stimulates the growth and differentiation of T cell response. Calcineurin is the target of a class of drugs called calcineurin inhibitors, which includes cyclosporine, pimecrolimus
Pimecrolimus
Pimecrolimus is an immunomodulating agent used in the treatment of atopic dermatitis . It is currently available as a topical cream, once marketed by Novartis under the trade name Elidel.-Pharmacology:Pimecrolimus is an ascomycin macrolactam derivative...
and tacrolimus
Tacrolimus
Tacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...
.
Mechanism of action
When an antigen-presenting cellAntigen-presenting cell
An antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...
interacts with a T cell receptor
T cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
on T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s, there is an increase in the cytoplasmic level of calcium, which activates calcineurin, by binding a regulatory subunit and activating calmodulin
Calmodulin
Calmodulin is a calcium-binding protein expressed in all eukaryotic cells...
binding. Calcineurin induces different transcription factors (NFAT
NFAT
Nuclear factor of activated T-cells is a general name applied to a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system...
s) 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 lymphocyte
Cytotoxic T cell
A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or...
s 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.
Schizophrenia
Calcineurin is linked to receptors for several brain chemicals including NMDANMDA
N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...
, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
. An experiment with genetically-altered mice that could not produce calcineurin showed similar symptoms as in humans with schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
: impairment in working memory
Working memory
Working memory has been defined as the system which actively holds information in the mind to do verbal and nonverbal tasks such as reasoning and comprehension, and to make it available for further information processing...
, attention deficits, aberrant social behavior, and several other abnormalities characteristic of schizophrenia.
Diabetes
Scientists believe that calcineurin might prove to be one of the two keys, along with NFAT, in improving the function of diabetics' pancreaticPancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
beta cells.
Calcineurin/Nfat signaling is required for perinatal lung maturation and function.
Interactions
Calcineurin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with DSCR1
DSCR1
Down syndrome critical region gene 1, also known as DSCR1, is a protein that in humans is encoded by the DSCR1 gene.- Function :The protein encoded by this gene interacts with calcineurin A and inhibits calcineurin-dependent signaling pathways of genetic transcription, possibly affecting central...
and AKAP5
AKAP5
A-kinase anchor protein 5 is an enzyme that in humans is encoded by the AKAP5 gene.-Interactions:AKAP5 has been shown to interact with Calcineurin and GABRB3.-Further reading:...
.