Endothelin-B receptors activate Gα13

1999 ◽  
Vol 276 (4) ◽  
pp. C930-C937 ◽  
Author(s):  
Kenichiro Kitamura ◽  
Naoki Shiraishi ◽  
William D. Singer ◽  
Mary E. Handlogten ◽  
Kimio Tomita ◽  
...  
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Guanine Nucleotides ◽  
Heterotrimeric G Proteins ◽  
Human Embryonic Kidney ◽  
Cellular Effects ◽  
293 Cells ◽  
Specific Antagonist ◽  
Α Chain ◽  
Endothelin B

Endothelin (ET) receptors activate heterotrimeric G proteins that are members of the Gi, Gq, and Gs families but may also activate members of other families such as Gα12/13. Gα13 has multiple complex cellular effects that are similar to those of ET. We studied the ability of ET receptors to activate Gα13 using an assay for G protein α-chain activation that is based on the fact that an activated (GTP-bound) α-chain is resistant to trypsinization compared with an inactive (GDP-bound) α-chain. Nonhydrolyzable guanine nucleotides and AlMgF protected Gα13 from degradation by trypsin. In membranes from human embryonic kidney 293 cells that coexpress ETB receptors and α13, ET-3 and 5′-guanylylimidodiphosphate [Gpp(NH)p] increased the protection of α13 compared with Gpp(NH)p alone. The specificity of ETBreceptor-α13 coupling was documented by showing that β2receptors and isoproterenol or ETAreceptors and ET-1 did not activate α13 and that a specific antagonist for ETB receptors blocked ET-3-dependent activation of α13.

scholarly journals Every Detail Matters. That Is, How the Interaction between Gα Proteins and Membrane Affects Their Function

Membranes ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 222
Author(s):  
Agnieszka Polit ◽  
Paweł Mystek ◽  
Ewa Błasiak
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
G Proteins ◽  
Lipid Membranes ◽  
Signaling Proteins ◽  
Heterotrimeric G Proteins ◽  
Membrane Attachment ◽  
The Individual ◽  
Multicellular Organisms ◽  
G Protein Coupled

In highly organized multicellular organisms such as humans, the functions of an individual cell are dependent on signal transduction through G protein-coupled receptors (GPCRs) and subsequently heterotrimeric G proteins. As most of the elements belonging to the signal transduction system are bound to lipid membranes, researchers are showing increasing interest in studying the accompanying protein–lipid interactions, which have been demonstrated to not only provide the environment but also regulate proper and efficient signal transduction. The mode of interaction between the cell membrane and G proteins is well known. Despite this, the recognition mechanisms at the molecular level and how the individual G protein-membrane attachment signals are interrelated in the process of the complex control of membrane targeting of G proteins remain unelucidated. This review focuses on the mechanisms by which mammalian Gα subunits of G proteins interact with lipids and the factors responsible for the specificity of membrane association. We summarize recent data on how these signaling proteins are precisely targeted to a specific site in the membrane region by introducing well-defined modifications as well as through the presence of polybasic regions within these proteins and interactions with other components of the heterocomplex.

scholarly journals Signaling from G Protein-coupled Receptors to ERK5/Big MAPK 1 Involves Gαqand Gα12/13Families of Heterotrimeric G Proteins

2000 ◽  
Vol 275 (28) ◽  
pp. 21730-21736 ◽  
Author(s):  
Shigetomo Fukuhara ◽  
Maria Julia Marinissen ◽  
Mario Chiariello ◽  
J. Silvio Gutkind
Keyword(s):  
G Protein ◽  
G Proteins ◽  
G Protein Coupled Receptors ◽  
Heterotrimeric G Proteins ◽  
G Protein Coupled

Regulation of Human Neuronal Calcium Channels by G Protein βγ Subunits Expressed in Human Embryonic Kidney 293 Cells

1997 ◽  
Vol 52 (2) ◽  
pp. 282-291 ◽  
Author(s):  
Lee R. Shekter ◽  
Ronald Taussig ◽  
Samantha E. Gillard ◽  
Richard J. Miller
Keyword(s):  
Calcium Channels ◽  
G Protein ◽  
Human Embryonic Kidney ◽  
293 Cells ◽  
Neuronal Calcium Channels

scholarly journals Physiological Regulation of G Protein-Linked Signaling

1999 ◽  
Vol 79 (4) ◽  
pp. 1373-1430 ◽  
Author(s):  
Andrew J. Morris ◽  
Craig C. Malbon
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Chemokine Receptors ◽  
Transcriptional Control ◽  
Heterotrimeric G Proteins ◽  
Protein Prenylation ◽  
Physiological Control ◽  
Physiological Regulation ◽  
Surface Receptors ◽  
Genes Encoding

Heterotrimeric G proteins in vertebrates constitute a family molecular switches that transduce the activation of a populous group of cell-surface receptors to a group of diverse effector units. The receptors include the photopigments such as rhodopsin and prominent families such as the adrenergic, muscarinic acetylcholine, and chemokine receptors involved in regulating a broad spectrum of responses in humans. Signals from receptors are sensed by heterotrimeric G proteins and transduced to effectors such as adenylyl cyclases, phospholipases, and various ion channels. Physiological regulation of G protein-linked receptors allows for integration of signals that directly or indirectly effect the signaling from receptor→G protein→effector(s). Steroid hormones can regulate signaling via transcriptional control of the activities of the genes encoding members of G protein-linked pathways. Posttranscriptional mechanisms are under physiological control, altering the stability of preexisting mRNA and affording an additional level for regulation. Protein phosphorylation, protein prenylation, and proteolysis constitute major posttranslational mechanisms employed in the physiological regulation of G protein-linked signaling. Drawing upon mechanisms at all three levels, physiological regulation permits integration of demands placed on G protein-linked signaling.

scholarly journals Heterotrimeric G-Proteins Are Indispensable for FLT3-ITD autophosphorylation and Oncogenic Function

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2712-2712
Author(s):  
Maike Rehage ◽  
Susanne Wingert ◽  
Nadine Haetscher ◽  
Sabrina Bothur ◽  
Hubert Serve ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
G Protein ◽  
G Proteins ◽  
B Cell Lymphoma ◽  
Physical Interaction ◽  
Heterotrimeric G Proteins ◽  
Leukemic Transformation ◽  
Hematopoietic Stem ◽  
Oncogenic Function

Abstract Heterotrimeric G-proteins transmit signals of G-protein coupled receptors and regulate many basic cellular functions. However, their role in normal and malignant hematopoietic stem cells remains obscure. Activating mutations in the heterotrimeric G-protein Gaq were found in various cancers and its expression is enhanced in diffuse large B-cell lymphoma and T-ALL. Our previous data suggested the involvement of heterotrimeric G-proteins in Flt3-ITD-mediated leukemic transformation. FMS-like tyrosine kinase 3 with internal tandem duplication (FLT3-ITD) is a frequent oncoprotein in acute myeloid leukemia causing constitutive active STAT5 signaling. Here, we investigated a novel role of Gaq in Flt3-ITD-induced leukemic transformation. We could show that Gaq is indispensable for aberrant FLT3-ITD activation and oncogenic function as Gaq activity is necessary to maintain the autophosphorylation of FLT3-ITD. Gaq abrogation resulted in diminished cell proliferation and colony formation as well as delayed leukemogenesis in vivo of Flt3-ITD leukemic cells. Importantly, the growth inhibition could be rescued by addition of IL3 and did not occur in the presence of FLT3 ligand-activated FLT3 wildtype receptor, demonstrating the specificity of Gaq requirement for FLT3-ITD oncogenic signaling. Interestingly, co-immunoprecipitations revealed a direct physical interaction between FLT3-ITD and Gaq which did not require phosphorylation of the receptor tyrosine kinase. Hence, FLT3-ITD hyperphosphorylation seems to be rather a consequence of the interaction than a prerequisite. Flt3-ITD-induced transformation of murine hematopoietic stem/progenitor cells (HSPCs) strictly depended on the presence of Gaq, and the ablation of Gaq/11 in transplanted Flt3-ITD-transduced HSPCs from conditional Gaq/11 double knock-out mice delayed leukemic burden. These findings of an unexpected, yet critical, role of Gaq place the molecule as an important target for antileukemic strategies. Disclosures No relevant conflicts of interest to declare.

Multiple mechanisms of receptor-G protein signaling specificity

1995 ◽  
Vol 269 (2) ◽  
pp. F141-F158 ◽  
Author(s):  
J. R. Raymond
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Linear Models ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Heterotrimeric G Proteins ◽  
Cellular Functions ◽  
Signaling Specificity ◽  
Intracellular Signals ◽  
Specific Manner

The hormone-receptor-G protein complex transduces extracellular information into intracellular signals that ultimately regulate cellular functions in a highly specific manner. There are hundreds of receptor types that transduce signals through a relatively limited repertoire of heterotrimeric G proteins. Linear models of signaling specificity that require specific and highly selective coupling of hormone to receptor to G protein have proven inadequate to explain how highly particular signals are funneled through the G protein "bottleneck." Recent studies have uncovered a plethora of mechanisms that contribute to signaling specificity. This review focuses on the mechanisms that contribute to specificity in the interactions of receptors with G proteins.

Ion Channels as G Protein Effectors

Physiology ◽  
1991 ◽  
Vol 6 (4) ◽  
pp. 158-161
Author(s):  
AM Brown
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Cell Signaling ◽  
G Protein ◽  
G Proteins ◽  
Heterotrimeric G Proteins ◽  
Regulatory Processes ◽  
Functional Implications

Signaling between cells may be accomplished or accompanied by changes in membrane potential. The latter is regulated by ion channels, which are targets for regulatory processes initiated during signaling. Cell signaling frequently involves heterotrimeric G proteins. Evidence that ion channels are G protein effectors and functional implications of such regulation are reviewed.

Abscisic acid induction of GTP hydrolysis in maize coleoptile plasma membranes

1998 ◽  
Vol 25 (5) ◽  
pp. 539 ◽  
Author(s):  
Helen R. Irving
Keyword(s):  
Abscisic Acid ◽  
G Protein ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Plasma Membranes ◽  
Dependent Manner ◽  
Gtpase Activity ◽  
Heterotrimeric G Proteins ◽  
Gtp Hydrolysis ◽  
Maize Coleoptile

Since receptor-coupled G proteins increase GTP hydrolysis (GTPase) activity upon ligands binding to the receptor, a study was undertaken to determine if abscisic acid (ABA) induced such an effect. Plasma membranes isolated from etiolated maize (Zea mays L.) coleoptiles were enriched in GTPase activity relative to microsomal fractions. Vanadate was included in the assay to inhibit the high levels of vanadate sensitive low affinity GTPases present. Under these conditions, GTPase activity was enhanced by Mg2+, stimulated by mastoparan, and inhibited by GTPγS indicating the presence of either monomeric or heterotrimeric G proteins. The combination of NaF and AlCl3 is expected to inhibit heterotrimeric G protein activity but had little effect on GTPase activity in maize coleoptile membranes. Cholera toxin enhanced basal GTPase activity, confirming the presence of heterotrimeric G proteins in maize plasma membranes. Pertussis toxin also slightly enhanced basal GTPase activity in maize membranes. Abscisic acid enhanced GTPase activity optimally at 5 mmol/L Mg2+ in a concentration dependent manner by 1.5-fold at 10 µmol/L and up to three-fold at 100 µmol/L ABA. Abscisic acid induced GTPase activity was inhibited by GTPγS, the combination of NaF and AlCl3, and pertussis toxin. Overall, these results are typical of a receptor-coupled G protein responding to its ligand.

Anesthetics Inhibit Acetylcholine-promoted Guanine Nucleotide Exchange of Heterotrimeric G Proteins of Airway Smooth Muscle

2004 ◽  
Vol 101 (1) ◽  
pp. 120-126 ◽  
Author(s):  
Chie Sakihara ◽  
William J. Perkins ◽  
David O. Warner ◽  
Keith A. Jones
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
G Protein ◽  
Muscarinic Receptor ◽  
G Proteins ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Contraction ◽  
Heterotrimeric G Proteins ◽  
Nucleotide Exchange ◽  
Heterotrimeric G Protein

Background Anesthetics inhibit airway smooth muscle contraction in part by a direct effect on the smooth muscle cell. This study tested the hypothesis that the anesthetics halothane and hexanol, which both relax airway smooth muscle in vitro, inhibit acetylcholine-promoted nucleotide exchange at the alpha subunit of the Gq/11 heterotrimeric G protein (Galphaq/11; i.e., they inhibit muscarinic receptor-Galphaq/11 coupling). Methods The effect of halothane (0.38 +/- 0.02 mm) and hexanol (10 mm) on basal and acetylcholine-stimulated Galphaq/11 guanosine nucleotide exchange was determined in membranes prepared from porcine tracheal smooth muscle. The nonhydrolyzable, radioactive form of guanosine-5'-triphosphate, [S]GTPgammaS, was used as the reporter for Galphaq/11 subunit dissociation from the membrane to soluble fraction, which was immunoprecipitated with rabbit polyclonal anti-Galphaq/11 antiserum. Results Acetylcholine caused a significant time- and concentration-dependent increase in the magnitude of Galphaq/11 nucleotide exchange compared with basal values (i.e., without acetylcholine), reaching a maximal difference at 100 microm (35.9 +/-2.9 vs. 9.8 +/-1.2 fmol/mg protein, respectively). Whereas neither anesthetic had an effect on basal Galphaq/11 nucleotide exchange, both halothane and hexanol significantly inhibited the increase in Galphaq/11 nucleotide exchange produced by 30 microm acetylcholine (by 59% and 68%, respectively). Conclusions Halothane and hexanol interact with the receptor-heterotrimeric G-protein complex in a manner that prevents acetylcholine-promoted exchange of guanosine-5(')-triphosphate for guanosine-5'-diphosphate at Galphaq/11. These data are consistent with the ability of anesthetics to interfere with cellular processes mediated by heterotrimeric G proteins in many cells, including effects on muscarinic receptor-G-protein regulation of airway smooth muscle contraction.

scholarly journals Plant hormone perception and action: a role for G–protein signal transduction?

1998 ◽  
Vol 353 (1374) ◽  
pp. 1425-1430 ◽  
Author(s):  
Richard Hooley
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
G Proteins ◽  
Plant Hormone ◽  
Higher Plants ◽  
Signalling Pathways ◽  
Heterotrimeric G Proteins ◽  
Extracellular Signals ◽  
G Protein Signalling ◽  
Auxin Signalling

Plants perceive and respond to a profusion of environmental and endogenous signals that influence their growth and development. The G–protein signalling pathway is a mechanism for transducing extracellular signals that is highly conserved in a range of eukaryotes and prokaryotes. Evidence for the existence of G–protein signalling pathways in higher plants is reviewed, and their potential involvement in plant hormone signal transduction evaluated. A range of biochemical and molecular studies have identified potential components of G–protein signalling in plants, most notably a homologue of the G–protein coupled receptor superfamily ( GCR1 ) and the G α and G β subunits of heterotrimeric G–proteins. G–protein agonists and antagonists are known to influence a variety of signalling events in plants and have been used to implicate heterotrimeric G–proteins in gibberellin and possibly auxin signalling. Antisense suppression of GCR1 in Arabidopsis leads to a phenotype which supports a role for this receptor in cytokinin signalling. These observations suggest that higher plants have at least some of the components of G–protein signalling pathways and that these might be involved in the action of certain plant hormones.

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