Genetics of Endocrine Disorders and Diabetes Mellitus
George H. Gass, Harold M. Kaplan in Handbook of Endocrinology, 2020
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
Congenital Hypothyroidism Associated with Thyrotropin Unresponsiveness
Geraldo Medeiros-Neto, John Bruton Stanbury in Inherited Disorders of the Thyroid System, 2019
The primary structure of the TSH receptor, deduced from the sequence of its cDNA, confirmed that it belongs to the G-coupled receptor family.16-18 It contains seven segments with a length compatible with that of transmembrane segments (Figure 1). The extracellular amino-terminal domain is particularly long, with 398 residues, and exhibits an imperfect repetition of a 25-residue leucine-rich motif.13 Six potential N-glycosylation sites are distributed along these leucine motifs. They may constitute domains implicated in protein-protein or protein-membrane interactions. The intracellular domain contains 346 residues with seven transmembrane segments that would play the role of a signal transducer, leading via G proteins to the activation of adenylyl cyclase.18 G proteins, as is discussed below, function as tranducers of information across the cell membrane by coupling receptors to effectors.21
Guanosine Triphosphate-Binding Proteins
Enrique Pimentel in Handbook of Growth Factors, 2017
G proteins are involved in the transmission of signals elicited by ligand-activated cell surface receptors across the plasma membrane. They have an important role in the mitogenic response of certain types of cells to hormones and growth factors. Incubation of mouse 3T3 cells with bombesin results in a concentration-dependent increase in the level of c-myc mRNA and stimulation of DNA synthesis, and these effects are totally abolished by pertussis toxin.50 By contrast, the mitogenic effects of PDGF on the same cells are not mediated by G proteins because these effects are not abolished by pertussis toxin, although PDGF also stimulates c-myc gene expression in the mouse cells. Thus, the mitogenic effects of bombesin-like growth factors appear to be mediated through a pertussis toxin-sensitive step involving G proteins, but the mitogenic effects of other growth factors may follow different pathways, not necessarily involving G proteins.
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.
Role of heterotrimeric G proteins in platelet activation and clot formation in platelets treated with integrin αIIbβ3 inhibitor
Published in Platelets, 2018
Ivan Budnik, Boris Shenkman, Hagit Hauschner, Isaac Zilinsky, Naphtali Savion
TRAP and acetylsalicylic acid (ASA; an inhibitor of cyclooxygenase) were obtained from Sigma-Aldrich (St. Louis, MO, USA); ADP was obtained from DiaMed (Cressier, Switzerland); U46619, a stable TXA2 analogue, AR-C66096, an inhibitor of P2Y12 ADP receptor coupled to Gαi2 protein, and MRS2500, an inhibitor of P2Y1 ADP receptor coupled to Gαq protein, were all obtained from Tocris Bioscience (Bristol, UK); Eptifibatide, a αIIbβ3 integrin inhibitor (Integrilin®), was obtained from Schering-Plough (Kenilworth, NJ, USA). The reagents were used at the following concentrations: TRAP 50 μM, ADP 1.25 μM, ASA 0.5 mM, AR-C66096 and MRS2500 10 μM, and U46619 1.5 and 0.1 μM. ASA was dissolved with DMSO. All other reagents were dissolved in saline. The corresponding amounts of DMSO and Tris-buffered saline (25 mM Tris, 150 mM NaCl, pH 7.4) were introduced in control samples. Approach to the G proteins’ signaling is presented in Table I.
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].
Related Knowledge Centers
- Gtpase
- Guanosine Diphosphate
- Heterotrimeric G Protein
- Monomer
- Small Gtpase
- Protein Family
- Molecular Switch
- Cell
- Guanosine Triphosphate
- Protein Complex