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
ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
A family of membrane PROTEINS that play a critical role in transmembrane signalling in the nervous system. G proteins, of which there are several forms, are named for their ability to bind small molecules called GUANINE NUCLEOTIDES, such as GUANINE TRIPHOSPHATE (GTP). In most synaptic transmission, two events occur when an external signal (such as a neurotransmitter or sensory stimulus) has an effect on cellular function. First, the external signal binds to its receptor on the outside of the neuronal membrane. When this occurs, GTP binds to the G protein on the internal surface of the membrane, which is linked to the RECEPTOR, thus making it active. Activation of the G protein regulates the levels of SECOND MESSENGERS, which in turn control the cascade of intracellular events ultimately leading to the cell's physiological response. There are two main types of G proteins: stimulatory G proteins (Gs), which activate transduction and inhibitory G proteins (Gi), which inhibit transduction. The G protein can also be directly coupled to an ION CHANNEL; in this case the activational state of the G protein regulates the permeability of certain ion channels. Although G proteins play many roles in cellular function, among their best known roles is controlling the intracellular levels of the second messenger CYCLIC AMP.
The endocrine system
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella in Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
The most common second messenger activated by the protein/peptide hormones and the catecholamines is cyclic adenosine monophosphate (cAMP). The pathway by which cAMP is formed and alters cellular function is illustrated in Figure 11.1. The process begins when the first messenger binds to its receptor. These receptors are quite large and span the bilayer of phospholipids within the plasma membrane. On the intracellular surface of the membrane, the receptor is associated with a protein called G protein, which serves as a transducer molecule. These proteins are referred to as G proteins because they bind with guanosine nucleotides. G protein acts as an intermediary between the receptor and the second messengers that will alter cellular activity. In an unstimulated cell, the inactive G protein binds guanosine diphosphate (GDP). When the hormone binds to its G protein-associated receptor, the G protein releases GDP, and becomes able to bind with guanosine triphosphate (GTP), which is found in the cytoplasm. Upon binding with the GTP, the now activated G protein loses its affinity for the receptor and increases its affinity for the plasma membrane-embedded enzyme, adenylyl cyclase. In turn, the adenylyl cyclase becomes activated and splits adenosine triphosphate (ATP) to form cAMP. The cAMP molecule serves as the second messenger that carries out the effects of the hormone inside the cell.
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].
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.
RGS7 silence protects palmitic acid-induced pancreatic β-cell injury by inactivating the chemokine signaling pathway
Published in Autoimmunity, 2023
Yurong Zhu, Jun Li, Tao Ba, Yuan Sun, Xiangyun Chang
Regulators of guanine nucleotide binding protein (G protein) signaling (RGSs) are originally identified as guanosine triphosphate (GTP)-activating proteins of Gα subunit of heterotrimer G protein [11]. Presently, more than 30 RGS proteins have been identified [12]. Of these, RGS7 is evolutionarily conservative in all animals and plays a key role in many processes and organ systems [13,14]. More importantly, RGS proteins were reported to play a key role in regulating insulin sensitivity in vivo [11,15–17]. RGS16 reconstitution substantially exacerbated insulin resistance in mice [18]. RGS7 is highly expressed in the brain, especially in the hypothalamus, and may be involved in regulating the hypothalamic–pituitary–adrenal axis in response to different stresses and stimuli [19]. Previous studies have provided evidence that RGS7 may constitute an obesity locus in humans [19,20]. Based on these findings, we speculated that RGS proteins may provide a new therapeutic opportunity for T2D.
Related Knowledge Centers
- Gtpase
- Guanosine Diphosphate
- Heterotrimeric G Protein
- Monomer
- Small Gtpase
- Protein Family
- Molecular Switch
- Cell
- Guanosine Triphosphate
- Protein Complex