Palmitoylation is required for signaling functions and membrane attachment of Gq alpha and Gs alpha.

Wedegaertner, Philip; Chu, David H.; Wilson, P.A.; Levis, Mark J.; Bourne, Henry R.

doi:10.1016/s0021-9258(19)74563-3

Cited by 280 publications

(87 citation statements)

References 50 publications

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“…Cardiac β-ARs interact with both Gαs and Gαi. Several members in β-AR signaling pathway are S-acylated in cardiomyocytes, such as β2-AR, Gαs, Gαi, and adenylyl cyclase 5/6 (Rybin et al, 2000;Ostrom et al, 2001;Steinberg and Brunton, 2001), and S-acylation of these proteins is crucial for subsequent functions (Thinon et al, 2016;Wedegaertner et al, 1993). The two major sub-types of β-ARs in mammalian hearts are the β1-AR and β2-AR.…”

Section: G Alpha Proteins and Beta-adrenergic Signalingmentioning

confidence: 99%

Regulation of Dynamic Protein S-Acylation

Chen

Fan

Boehning

2021

Front. Mol. Biosci.

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Protein S-acylation is the reversible addition of fatty acids to the cysteine residues of target proteins. It regulates multiple aspects of protein function, including the localization to membranes, intracellular trafficking, protein interactions, protein stability, and protein conformation. This process is regulated by palmitoyl acyltransferases that have the conserved amino acid sequence DHHC at their active site. Although they have conserved catalytic cores, DHHC enzymes vary in their protein substrate selection, lipid substrate preference, and regulatory mechanisms. Alterations in DHHC enzyme function are associated with many human diseases, including cancers and neurological conditions. The removal of fatty acids from acylated cysteine residues is catalyzed by acyl protein thioesterases. Notably, S-acylation is now known to be a highly dynamic process, and plays crucial roles in signaling transduction in various cell types. In this review, we will explore the recent findings on protein S-acylation, the enzymatic regulation of this process, and discuss examples of dynamic S-acylation.

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Section: G Alpha Proteins and Beta-adrenergic Signalingmentioning

confidence: 99%

Regulation of Dynamic Protein S-Acylation

Chen

Fan

Boehning

2021

Front. Mol. Biosci.

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“…Interestingly, many proteins of the GPCR signaling pathway undergo this modification. Palmitoyl moiety can be attached to certain GPCRs [47], Gα subunits [48,49], regulator of G protein signal (RGS) and its binding protein-R7BP [25,50], phosphodiesterase [51], and G protein-coupled receptor kinases (GRKs) [52][53][54]. It seems that the importance of palmitoylation is not limited to membrane localization.…”

Section: Palmitoylationmentioning

confidence: 99%

“…For Gα13, which is palmitoylated thrice, two palmitoylation sites were examined and shown to be necessary for attachment and receptor-G protein interaction [62]. Two palmitoyl anchors are significant for the localization of Gαq and signal transmission followed by receptor activation [49]. Yet, a single anchored Gαq mutant is capable of efficient signal transduction from the α2-adrenoreceptor [49].…”

Section: Palmitoylationmentioning

confidence: 99%

“…Two palmitoyl anchors are significant for the localization of Gαq and signal transmission followed by receptor activation [49]. Yet, a single anchored Gαq mutant is capable of efficient signal transduction from the α2-adrenoreceptor [49]. During the palmitoylation-depalmitoylation cycle, the protein commutes between the plasma membrane and the Golgi [63].…”

Section: Palmitoylationmentioning

confidence: 99%

“…Initial reports on the role of palmitoylation of the Gαs subunit provide contrary information. Wedegaertner and colleagues determined that non-S-palmitoylatable Gαs mutant localizes mainly in the cytosol with negligible cAMP generation after receptor stimulation [49]. On the other hand, other researchers demonstrated that the lack of S-palmitoylation and the deletion of the following helix region do not disrupt plasma membrane localization of Gαs [65,66].…”

Section: Palmitoylationmentioning

confidence: 99%

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

2021

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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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G Proteins in Signal Transduction

Birnbaumer

1995

Biomembranes

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Palmitoylation is required for signaling functions and membrane attachment of Gq alpha and Gs alpha.

Cited by 280 publications

References 50 publications

Regulation of Dynamic Protein S-Acylation

Regulation of Dynamic Protein S-Acylation

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

G Proteins in Signal Transduction

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