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Neurotransmitters and Receptors, Ion Channels, G Proteins and Second Messengers
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
G proteins are large heterotrimeric proteins consisting of α, β and γ subunits which act as transducers to bring about intracellular changes from an extracellular signal by modulating membrane ion channels or cellular enzymes. They are called G proteins because the α subunit can bind to both guanosine diphosphate (GDP) and GTP. Inactive GDP is bound to the α subunit.
Dopamine Receptors, Signaling Pathways, and Drugs
Published in Nira Ben-Jonathan, Dopamine, 2020
G proteins consist of three functional subunits: α, β, and γ. By some estimates, there are 15 α-subunits, 5 β-subunits, and 14 γ-subunits. The α-subunits are grouped by their sequence and functional similarities into the following categories: (1) Gαs (activation of AC), (2) Gαi/olf (inhibition of certain AC isoforms), (3) Gqα11 (activation of phospholipase β), (4) Gα12 (activation of membrane Rho kinase), and (5) Gα13 (activation of GC). Each α-subunit contains a guanine nucleotide-binding site. When inactive, the α-subunit is bound to GDP and to the βγ-complex, together forming a trimeric protein complex. Table 2.1 provides a list of the general features of the α-subunits with representative effectors, second messengers, and common effects.
Genetics of Endocrine Disorders and Diabetes Mellitus
Published in George H. Gass, Harold M. Kaplan, Handbook of Endocrinology, 2020
Bess Adkins Marshall, Abby Solomon Hollander
The G proteins are a family of proteins that couple cell-surface receptors for a variety of extracellular signals to enzymes or ion channels, resulting in the generation of an intracellular second messenger.8 In the inactive state, G proteins are heterotrimers consisting of α, β, and γ subunits. The α subunits bind guanine nucleotide, and the β and γ subunits form stable noncovalent heterodimers that are tightly associated with cell membranes. The inactive G protein has an a subunit associated with a β-γ complex and has GDP bound to the guanine nucleotide binding site. Activation of a G protein may occur when a ligand binds to its receptor. GTP is exchanged for GDP on the α subunit, and the α subunit dissociates form the β-γ complex. The free GTP-bound α subunit then dirctly interacts with and modulates its appropriate effector.8
The role of Gα protein signaling in the membrane estrogen receptor-mediated signaling
Published in Gynecological Endocrinology, 2021
Shuhui Zheng, Lin Wu, Chao Fan, Jingxia Lin, Yaxing Zhang, Tommaso Simoncini, Xiaodong Fu
There are 16 Gα genes in the human genome, encoding 23 known Gα proteins. According to the sequence similarity, these proteins can be divided into four categories: Gα (s/OLF), Gα(I1/I2/I3/O/T-rod/t-cone/gust/z), Gα (Q/11/14/16) and Gα (12/13) [13]. G-proteins can be regarded as molecular switches. They turn on the further signaling cascades respond to the GPCRs’ activation by extracellular stimuli. Various ligands can bind to GPCRs and active G-protein, such as photons, many hormones, and neurotransmitters. In addition, some non-GPCR proteins can also regulate G protein, such as Ric-8 protein, GPR-domain containing proteins, GBA-motif containing proteins, and RGS-domain-containing proteins. The switching function of G-proteins depends on the Gα’s ability to cycle between an inactive GDP-bound and an active GTP-bound state. Agonists binding to GPCRs promote the release of bound GDP from Gα [39]. Then the nucleotide-free Gα binds to GTP, leading to the dissociation of G βγ. The downstream signaling is initiated by both GTP-bound Gα and free Gβγ through interacting with downstream effectors.
A review of antibody-based therapeutics targeting G protein-coupled receptors: an update
Published in Expert Opinion on Biological Therapy, 2020
GPCRs play a key role in tissue and cell physiology, as well as homeostasis, and are implicated in various diseases including cancer, immune-mediated and inflammatory disorders, cardiovascular disease, infectious disease, as well as neurological and metabolic diseases. GPCRs respond to a wide variety of ligands, including biogenic amines, amino acids, nucleosides/nucleotides, ions, pH, pheromones, odourants, metabolites, lipids, glycoproteins, protease, peptides, and large proteins [5]; in fact, some receptors can be activated by more than one ligand (receptor promiscuity), for example, a number of the chemokine receptors possess more than one peptide ligand. Typically, activation causes a conformational change in the receptor which enables intracellular engagement of the G protein and then subsequent activation of downstream signaling pathways resulting in diverse cellular responses. Thus, aberrant signaling, mutations in GPCRs or G proteins play an important part in various diseases.
Genetic and molecular determinants of prostate cancer among Iranian patients: An update
Published in Critical Reviews in Clinical Laboratory Sciences, 2020
Majid Ghayour-Mobarhan, Gordon A. Ferns, Meysam Moghbeli
The G protein coupled receptor (GPCR) family are cell surface receptors involved in a variety of cellular processes. G proteins are mediators that transfer the signals from the cell surface receptor to intracellular signaling pathways involved in cell growth and transcription [31]. Prostate-specific G-protein coupled receptor (PSGR) is expressed mainly in human prostate epithelium, which is upregulated in PCa [32]. PSGR upregulation is synergistically associated with phosphatase and tensin homolog (PTEN) loss during PCa progression and metastasis [33]. LGR4, a member of the GPCRs, is involved in epithelial mesenchymal transition (EMT) and metastasis of PCa cells through the PI3K/Akt signaling pathway [34,35]. Moreover, GPR160 is associated with apoptosis and cell cycle arrest; GPR160 silencing significantly increased the levels of CASP1 in PCa cells [36]. Initial GPCR signal transduction is triggered by activation of heterotrimeric G proteins, which activate messenger systems, small GTPases, and kinase cascades. These proteins are composed of several subunits (α, β, and γ). The G protein subunit beta 3 (GNB3) encodes the β3 subunit of G proteins [37]. When the role of rs5443 single nucleotide polymorphisms (SNP) in PCa progression was evaluated in a subpopulation of Iranian patients, a significant correlation between PCa and T allele of the GNB3 C825T SNP was observed. Moreover, the presence of the GNB3 825 T allele was significantly related to tumor grade and stage [38].