PPP1R14A
Encyclopedia
Protein phosphatase 1 regulatory subunit 14A also known as CPI-17 (C-kinase potentiated Protein phosphatase-1 Inhibitor Mr = 17 kDa) is a protein
that in humans is encoded by the PPP1R14A gene
.
-dependent inhibitor protein of smooth muscle myosin phosphatase
, discovered in pig aortic homogenetes. Phosphorylation of the Thr
-38 residue converts the protein into a potent inhibitor for myosin phosphatase. A single phosphorylation of CPI-17 at Thr-38 triggers a global conformational change that causes re-alignment of four helices. Multiple kinases are identified to phosphorylate CPI-17, such as PKC
, ROCK, PKN
, ZIPK, ILK
, and PAK
. Agonist stimulation of smooth muscle enhances CPI-17 phosphorylation mainly through PKC and ROCK. Myosin phosphatase inhibition increases myosin phosphorylation and smooth muscle contraction in the absence of increased intracellular Ca2+ concentration. This phenomenon is known as Ca2+ sensitization, which occurs in response to agonist stimulation of smooth muscle. In Purkinje neuron, CPI-17 is involved in long-term synaptic depression.
There are three homologues of CPI-17:
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...
that in humans is encoded by the PPP1R14A gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
CPI-17 is a phosphorylationPhosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
-dependent inhibitor protein of smooth muscle myosin 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...
, discovered in pig aortic homogenetes. Phosphorylation of the Thr
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
-38 residue converts the protein into a potent inhibitor for myosin phosphatase. A single phosphorylation of CPI-17 at Thr-38 triggers a global conformational change that causes re-alignment of four helices. Multiple kinases are identified to phosphorylate CPI-17, such as PKC
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...
, ROCK, PKN
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...
, ZIPK, ILK
Integrin-linked kinase
Integrin-linked kinase is a 59kDa protein originally identified while conducting a yeast-two hybrid screen with integrin β1 as the bait protein...
, and PAK
P21 activated kinases
p21 activated kinases are members of a family of enzymes. They serve as targets for the small GTP binding proteins CDC42 and Rac and have been implicated in a wide range of biological activities.Members include:...
. Agonist stimulation of smooth muscle enhances CPI-17 phosphorylation mainly through PKC and ROCK. Myosin phosphatase inhibition increases myosin phosphorylation and smooth muscle contraction in the absence of increased intracellular Ca2+ concentration. This phenomenon is known as Ca2+ sensitization, which occurs in response to agonist stimulation of smooth muscle. In Purkinje neuron, CPI-17 is involved in long-term synaptic depression.
There are three homologues of CPI-17:
- Phosphatase Holoenzyme Inhibitor (PHI: PPP1R14BPPP1R14BProtein phosphatase 1 regulatory subunit 14B is an enzyme that in humans is encoded by the PPP1R14B gene.-Further reading:...
), - Kinase Enhanced Phosphatase Inhibitor (KEPI: PPP1R14CPPP1R14CProtein phosphatase 1 regulatory subunit 14C is an enzyme that in humans is encoded by the PPP1R14C gene.-Further reading:...
), and - Gastric-Brain Phosphatase Inhibitor (GBPI: PPP1R14D).