G-protein coupled receptor kinases
Encyclopedia
G protein-coupled receptor kinases (GRKs, GPCRKs) are a family
of protein kinase
s which regulate the activity of G protein-coupled receptors (GPCRs) by phosphorylating
their intracellular
domains after their associated G proteins have been released and activated. In other words, these protein
s are the mediators of tolerance related to GPCRs via up- and downregulation.
The phosphorylated serine
and threonine
residues act as binding site
s for arrestin
proteins which prevent the reassociation of the G proteins with their receptors, thereby preventing reactivation of the signaling pathway
.
GRK1 is involved with Rhodopsin phosphorlylation and deactivation. Defects in GRK1 result in Oguchi disease 2.
Protein family
A protein family is a group of evolutionarily-related proteins, and is often nearly synonymous with gene family. The term protein family should not be confused with family as it is used in taxonomy....
of protein kinase
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...
s which regulate the activity of G protein-coupled receptors (GPCRs) by phosphorylating
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
their intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
domains after their associated G proteins have been released and activated. In other words, these protein
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...
s are the mediators of tolerance related to GPCRs via up- and downregulation.
The phosphorylated serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
and threonine
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...
residues act as binding site
Binding site
In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...
s for arrestin
Arrestin
Arrestins are a small family of proteins important for regulating signal transduction.-Function:Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of G protein-coupled receptors in the visual rhodopsin system by Hermann Kühn and co-workers and...
proteins which prevent the reassociation of the G proteins with their receptors, thereby preventing reactivation of the signaling pathway
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
.
GRK1 is involved with Rhodopsin phosphorlylation and deactivation. Defects in GRK1 result in Oguchi disease 2.
Types of GRKs
| Name | Notes | 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... |
OMIM >- | G protein-coupled receptor kinase 1 |
Rhodopsin kinase Rhodopsin kinase Rhodopsin kinase is a serine/threonine-specific protein kinase involved in phototransduction.-See also:* Rhodopsin* Beta adrenergic receptor kinase* G-protein coupled receptor kinases-External links:... |
>- | β-Adrenergic receptor kinase 1 Beta adrenergic receptor kinase Beta adrenergic receptor kinase is a serine/threonine intracellular kinase. It is activated by PKA and its target is the beta adrenergic receptor... (BARK1) |
(GRK2) | >- | β-Adrenergic receptor kinase 2 Beta adrenergic receptor kinase Beta adrenergic receptor kinase is a serine/threonine intracellular kinase. It is activated by PKA and its target is the beta adrenergic receptor... (BARK2) |
(GRK3) | >- | Has been associated with regulation of kidney Kidney The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and... tubule Tubule A tubule is a very small tube or fistular structure.A system of surface-connected membranes in muscle that enables a nerve impulse to travel to the interior of the muscle fibre.In anatomy, a tubule is a minute tube lined with glandular epithelium.... function |
>- | Knockout mice have altered core body temperature | >- | Knockout mice are supersensitive to dopaminergic Dopaminergic Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine... s |
>- | Cone opsin kinase |
See also
- Downregulation and upregulationDownregulation and upregulationDownregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable...
- G protein-coupled receptorG protein-coupled receptorG protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
- PhosphorylationPhosphorylationPhosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
- Protein kinaseProtein kinaseA 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...