heterotrimeric G protein
Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a heterotrimeric complex. The biggest non-structu ...
alpha subunits. This family is also commonly called the Gq/11 (Gq/G11) family or Gq/11/14/15 family to include closely related family members. G alpha subunits may be referred to as Gq alpha, Gαq, or Gqα.
Gq proteins couple to
G protein-coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
s to activate beta-type phospholipase C (PLC-β) enzymes. PLC-β in turn hydrolyzes
phosphatidylinositol 4,5-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number o ...
(PIP2) to
diacyl glycerol
A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as su ...
(DAG) and
inositol trisphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the p ...
(IP3). IP3 acts as a
second messenger
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...
to release stored calcium into the cytoplasm, while DAG acts as a second messenger that activates protein kinase C (PKC).
Family members
In humans, there are four distinct proteins in the Gq alpha subunit family:
* Gαq is encoded by the gene
GNAQ
Guanine nucleotide-binding protein G(q) subunit alpha is a protein that in humans is encoded by the ''GNAQ'' gene. Together with GNA11 (its paralogue), it functions as a Gq alpha subunit.
Function
Guanine nucleotide-binding proteins are a fam ...
.
* Gα11 is encoded by the gene
GNA11
Guanine nucleotide-binding protein subunit alpha-11 is a protein that in humans is encoded by the ''GNA11'' gene. Together with GNAQ (its paralogue), it functions as a Gq alpha subunit.GNA14
Guanine nucleotide-binding protein subunit alpha-14 is a protein that in humans is encoded by the ''GNA14'' gene.GNA15
Guanine nucleotide-binding protein subunit alpha-15 is a protein that in humans is encoded by the ''GNA15'' gene.intracellular signaling pathways in response to activation of cell surface G protein-coupled receptors (GPCRs). GPCRs function as part of a three-component system of receptor-transducer-effector. The transducer in this system is a
heterotrimeric G protein
Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a heterotrimeric complex. The biggest non-structu ...
, composed of three subunits: a Gα protein such as Gαq, and a complex of two tightly linked proteins called Gβ and Gγ in a Gβγ complex. When not stimulated by a receptor, Gα is bound to guanosine diphosphate (GDP) and to Gβγ to form the inactive G protein trimer. When the receptor binds an activating ligand outside the cell (such as a
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
guanine nucleotide exchange factor
Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated struc ...
to promote GDP release from and guanosine triphosphate (GTP) binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ. Recent evidence suggests that Gβγ and Gαq-GTP could maintain partial interaction via the N-α-helix region of Gαq. GTP-bound Gα and Gβγ are then freed to activate their respective downstream signaling enzymes.
Gq/11/14/15 proteins all activate beta-type phospholipase C (PLC-β) to signal through calcium and PKC signaling pathways. PLC-β then cleaves a specific plasma membranephospholipid,
phosphatidylinositol 4,5-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number o ...
(PIP2) into
diacyl glycerol
A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as su ...
(DAG) and
inositol 1,4,5-trisphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the ...
(IP3). DAG remains bound to the membrane, and IP3 is released as a soluble molecule into the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
. IP3 diffuses to bind to IP3 receptors, a specialized
calcium channel
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels.
Comparison tables
The following tables e ...
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
and only allow the passage of calcium from the ER into the cytoplasm. Since cells actively sequester calcium in the ER to keep cytoplasmic levels low, this release causes the cytosolic concentration of calcium to increase, causing a cascade of intracellular changes and activity through calcium binding proteins and calcium-sensitive processes.
: ''Further reading:
Calcium function in vertebrates
Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contractio ...
''
DAG works together with released calcium to activate specific isoforms of PKC, which are activated to phosphorylate other molecules, leading to further altered cellular activity.
: ''Further reading: function of protein kinase C''
The Gαq / Gα11 (Q209L) mutation is associated with the development of uveal melanoma and its pharmacological inhibition (cyclic depsipeptide FR900359 inhibitor), decreases tumor growth in preclinical trials.
Receptors
The following
G protein-coupled receptors
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
Alpha-1 adrenergic receptor
alpha-1 (α1) adrenergic receptors are G protein-coupled receptors (GPCRs) associated with the Gq heterotrimeric G protein. α1-adrenergic receptors are subdivided into three highly homologous subtypes, i.e., α1A-, α1B-, and α1D-adrenerg ...
Angiotensin II receptor type 1
Angiotensin II receptor type 1 (AT1) is the best characterized angiotensin receptor. It is encoded in humans by the ''AGTR1'' gene. AT1 has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pre ...
*
Calcitonin receptor
The calcitonin receptor (CT) is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism.
CT works by activating the ...
*
Histamine H1 receptor
The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the h ...
*
Metabotropic glutamate receptor
The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate re ...
muscarinic receptors
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...
*
Trace amine-associated receptor 1
Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...
At least some Gq-coupled receptors (e.g., the muscarinic acetylcholine M3 receptor) can be found preassembled (pre-coupled) with Gq. The common polybasic domain in the C-tail of Gq-coupled receptors appears necessary for this receptor¬G protein preassembly.
See also
*
Second messenger system
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...
*
G protein-coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
*
Heterotrimeric G protein
Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a heterotrimeric complex. The biggest non-structu ...
Calcium signaling
Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allos ...
Gs alpha subunit
The Gs alpha subunit (Gαs, Gsα) is a subunit of the heterotrimeric G protein Gs that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. Gsα is a GTPase that functions as a cellular signaling protein.
Gsα is the founding ...
G12/G13 alpha subunits
G12/G13 alpha subunits are alpha subunits of heterotrimeric G proteins that link cell surface G protein-coupled receptors primarily to guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton. Together, ...