Dynamic Coupling and Allosteric Networks in the Alpha Subunit of Heterotrimeric G Proteins

Small G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form guanosine diphosphate (GDP). The best-known members are the Ras GTPases and hence they are sometimes called Ras subfamily GTPases.

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G-Alpha Subunit Abundance and Activity Differentially Regulate β-Catenin Signaling

Molecular and Cellular Biology ◽

10.1128/mcb.00422-18 ◽

2018 ◽

Vol 39 (5) ◽

Cited By ~ 1

Author(s):

Arshiya Banu ◽

Karen J. Liu ◽

Alistair J. Lax ◽

Agamemnon E. Grigoriadis

Keyword(s):

G Proteins ◽

Pasteurella Multocida ◽

Alpha Subunit ◽

Dependent Manner ◽

Heterotrimeric G Proteins ◽

Wild Type ◽

Content Type ◽

Alpha Subunits ◽

Licl Treatment ◽

Signal Transduction Proteins

ABSTRACT Heterotrimeric G proteins are signal transduction proteins involved in regulating numerous signaling events. In particular, previous studies have demonstrated a role for G-proteins in regulating β-catenin signaling. However, the link between G-proteins and β-catenin signaling is controversial and appears to depend on G-protein specificity. We describe a detailed analysis of a link between specific G-alpha subunits and β-catenin using G-alpha subunit genetic knockout and knockdown approaches. The Pasteurella multocida toxin was utilized as a unique tool to activate G-proteins, with LiCl treatment serving as a β-catenin signaling agonist. The results show that Pasteurella multocida toxin (PMT) significantly enhanced LiCl-induced active β-catenin levels in HEK293T cells and mouse embryo fibroblasts. Evaluation of the effect of specific G-alpha proteins on the regulation of β-catenin showed that Gq/11 and G12/13 knockout cells had significantly higher levels of active and total β-catenin than wild-type cells. The stimulation of active β-catenin by PMT and LiCl was lost upon both constitutive and transient knockdown of G12 and G13 but not Gq. Based on our results, we conclude that endogenous G-alpha proteins are negative regulators of active β-catenin; however, PMT-activated G-alpha subunits positively regulate LiCl-induced β-catenin expression in a G12/13-dependent manner. Hence, G-alpha subunit regulation of β-catenin is context dependent.

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Domain-Opening and Dynamic Coupling in the α-Subunit of Heterotrimeric G Proteins

Biophysical Journal ◽

10.1016/j.bpj.2013.06.006 ◽

2013 ◽

Vol 105 (2) ◽

pp. L08-L10 ◽

Cited By ~ 13

Author(s):

Xin-Qiu Yao ◽

Barry J. Grant

Keyword(s):

G Proteins ◽

Heterotrimeric G Proteins ◽

Dynamic Coupling ◽

Α Subunit

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Faculty Opinions recommendation of SIGNAL TRANSDUCTION. Structural basis for nucleotide exchange in heterotrimeric G proteins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725571385.793507860 ◽

2015 ◽

Author(s):

Bert de Groot

Keyword(s):

Signal Transduction ◽

G Proteins ◽

Structural Basis ◽

Heterotrimeric G Proteins ◽

Nucleotide Exchange

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Heterotrimeric G-proteins

Encyclopedic Reference of Molecular Pharmacology ◽

10.1007/3-540-29832-0_761 ◽

2006 ◽

pp. 451-451

Keyword(s):

G Proteins ◽

Heterotrimeric G Proteins

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Olfactory desensitization requires membrane targeting of receptor kinase mediated by beta gamma-subunits of heterotrimeric G proteins.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)42306-4 ◽

1994 ◽

Vol 269 (1) ◽

pp. 37-40

Author(s):

I. Boekhoff ◽

J. Inglese ◽

S. Schleicher ◽

W.J. Koch ◽

R.J. Lefkowitz ◽

...

Keyword(s):

G Proteins ◽

Membrane Targeting ◽

Heterotrimeric G Proteins ◽

Receptor Kinase ◽

Gamma Subunits

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

Membranes ◽

10.3390/membranes11030222 ◽

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.

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