The G
s alpha subunit (G
αs, G
sα) is a subunit of the
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 Heteromer, heterotrimeric complex. The biggest no ...
G
s that stimulates the
cAMP-dependent pathway
In the field of molecular biology, the cAMP-dependent pathway, also known as the adenylyl cyclase pathway, is a G protein-coupled receptor-triggered signaling cascade used in cell communication.
Discovery
cAMP was discovered by Earl Sutherland ...
by activating
adenylyl cyclase
Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction:
:A ...
. G
sα is a
GTPase
GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a pro ...
that functions as a cellular signaling protein.
G
sα is the founding member of one of the four families of heterotrimeric G proteins, defined by the
alpha subunits they contain: the G
αs family,
Gαi/Gαo family,
Gαq family, and
Gα12/Gα13 family.
The Gs-family has only two members: the other member is G
olf, named for its predominant expression in the olfactory system. In humans, G
sα is encoded by the
GNAS complex locus, while G
olfα is encoded by the
GNAL
Guanine nucleotide-binding protein G(olf) subunit alpha is a protein that in humans is encoded by the ''GNAL'' gene.
Its main product is the heterotrimeric G-protein alpha subunit Golf-α, a member of the Gs alpha subunit family that is a key compo ...
gene.
Function
The general function of G
s is to activate
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 Heteromer, heterotrimeric complex. The biggest no ...
, composed of three subunits: a Gα protein such as G
sα, 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
GDP
Gross domestic product (GDP) is a monetary measure of the market value of all the final goods and services produced and sold (not resold) in a specific time period by countries. Due to its complex and subjective nature this measure is ofte ...
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 ...
or
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
), the activated receptor acts as a
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 structu ...
to promote GDP release from and
GTP binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ.
In particular, GTP-bound, activated G
sα binds to
adenylyl cyclase
Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction:
:A ...
to produce the
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 ...
cAMP
Camp may refer to:
Outdoor accommodation and recreation
* Campsite or campground, a recreational outdoor sleeping and eating site
* a temporary settlement for nomads
* Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
, which in turn activates the
cAMP-dependent protein kinase (also called Protein Kinase A or PKA).
Cellular effects of G
sα acting through PKA are described
here
Here is an adverb that means "in, on, or at this place". It may also refer to:
Software
* Here Technologies, a mapping company
* Here WeGo (formerly Here Maps), a mobile app and map website by Here Technologies, Here
Television
* Here TV (form ...
.
Although each GTP-bound G
sα can activate only one adenylyl cyclase enzyme, amplification of the signal occurs because one receptor can activate multiple copies of G
s while that receptor remains bound to its activating
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
, and each G
sα-bound adenylyl cyclase enzyme can generate substantial cAMP to activate many copies of PKA.
Receptors
The G protein-coupled receptors that couple to the G
s family proteins include:
*
5-HT receptors types
5-HT4 and
5-HT7
*
ACTH receptor
The adrenocorticotropic hormone receptor or ACTH receptor also known as the melanocortin receptor 2 or MC2 receptor is a type of melanocortin receptor (type 2) which is specific for ACTH. A G protein–coupled receptor located on the external ...
a.k.a. MC2R
*
Adenosine receptor
The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand. There are four known types of adenosine receptors in humans: A1, A2A, A2B and A3; each is encoded by a di ...
types
A2a and
A2b
*
Arginine vasopressin receptor 2
Vasopressin receptor 2 (V2R), or arginine vasopressin receptor 2 (officially called AVPR2), is a protein that acts as receptor for vasopressin. AVPR2 belongs to the subfamily of G-protein-coupled receptors. Its activity is mediated by the Gs ty ...
*
β-adrenergic receptors types
β1,
β2 and
β3
*
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 ...
*
Calcitonin gene-related peptide receptor
Calcitonin receptor-like (CALCRL), also known as the calcitonin receptor-like receptor (CRLR), is a human protein; it is a receptor for calcitonin gene-related peptide.
Function
The protein encoded by the CALCRL gene is a G protein-coupled rec ...
*
Cannabinoid receptor 2
The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the ''CNR2'' gene. It is closely related to the cannabinoid receptor type 1 (CB1), which is la ...
*
Corticotropin-releasing hormone receptor
Corticotropin-releasing hormone receptors (CRHRs), also known as corticotropin-releasing factor receptors (CRFRs) are a G protein-coupled receptor family that binds corticotropin-releasing hormone (CRH). There are two receptors in the family, ...
*
Dopamine receptors
Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...
D
1-like family (
D1 and
D5), mainly through G
olf in the
striatum
The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...
*
FSH-receptor
*
Gastric inhibitory polypeptide receptor
The gastric inhibitory polypeptide receptor (GIP-R), also known as the glucose-dependent insulinotropic polypeptide receptor, is a protein that in humans is encoded by the ''GIPR'' gene. GIP-R is a member of the 7-transmembrane protein family, a ...
*
Glucagon receptor
The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in the ...
*
Growth-hormone-releasing hormone receptor
*
Histamine H2 receptor
*
Luteinizing hormone/choriogonadotropin receptor
The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR) is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonad ...
*
Melanocortin receptor
Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors.
There are five known members of the melanocortin receptor system each with differing specificities for melanocortins:
* . MC1R is associat ...
:
MC1R
The melanocortin 1 receptor (MC1R), also known as melanocyte-stimulating hormone receptor (MSHR), melanin-activating peptide receptor, or melanotropin receptor, is a G protein–coupled receptor that binds to a class of pituitary peptide hormones ...
,
MC2R
The adrenocorticotropic hormone receptor or ACTH receptor also known as the melanocortin receptor 2 or MC2 receptor is a type of melanocortin receptor (type 2) which is specific for ACTH. A G protein–coupled receptor located on the external cel ...
(a.k.a. ACTH receptor),
MC3R
Melanocortin 3 receptor (MC3R) is a protein that in humans is encoded by the gene.
Function
This gene encodes MC3R, a G-protein coupled receptor (GPCR) for melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) that is exp ...
,
MC4R,
MC5R
*
Olfactory receptors
Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (for example, compounds that have an odor) which give ri ...
, through G
olf in the
olfactory neurons
*
Parathyroid hormone receptor 1
Parathyroid hormone/parathyroid hormone-related peptide receptor, also known as parathyroid hormone 1 receptor (PTH1R), is a protein that in humans is encoded by the ''PTH1R'' gene. PTH1R functions as a receptor for parathyroid hormone ( PTH) and f ...
*
Prostaglandin receptor Prostaglandin receptors or prostanoid receptors represent a sub-class of cell surface membrane Receptor (biochemistry), receptors that are regarded as the primary receptors for one or more of the classical, naturally occurring prostanoids viz., pros ...
types
D2 and
I2
*
Secretin receptor
Human secretin receptor (gene name SCTR) is a G protein-coupled receptor which binds secretin and is the leading member (''i.e.'', first cloned) of the class B GPCR subfamily.
Interactions
Secretin receptor has been shown to interact with pitui ...
*
Thyrotropin receptor
The thyrotropin receptor (or TSH receptor) is a receptor (and associated protein) that responds to thyroid-stimulating hormone (also known as "thyrotropin") and stimulates the production of thyroxine (T4) and triiodothyronine (T3). The TSH recep ...
*
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 ...
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 Heteromer, heterotrimeric complex. The biggest no ...
*
Adenylyl cyclase
Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction:
:A ...
*
Protein kinase A
In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, including regulatio ...
*
Gi alpha subunit
Gi protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the Gi/o (Gi /Go ) family or Gi/o/z/t family to include closely related family members. G alpha subunits may be referred ...
*
Gq alpha subunit
Gq protein alpha subunit is a family of heterotrimeric G protein 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 ...
*
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, ...
References
External links
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Peripheral membrane proteins
Medical mnemonics