Structural Determinants for Phosphatidic Acid Regulation of Phospholipase C-β1

Ross, Elliott M.; Mateu, Dania; Gomes, Aldrin V.; Arana, Carlos; Tran, Thanh; Litosch, Irene

doi:10.1074/jbc.m606487200

Cited by 32 publications

(30 citation statements)

References 39 publications

(60 reference statements)

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“…Comparing a model structure of PH-β2 with the known structure of PH-δ1 suggests that the β5/β6 loop, which is longer than in PH-δ1, (Figure 3) could act as a regulatory domain for activation by Gβγ [41]. A peptide corresponding to this loop (PHβ [71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] ) activates the enzyme, and this activation is competitive with Gβγ activation. The structure of PLC-β2 reveals that the β5/β6 loop does not belong to the surface that is tightly packed with the EF-hands and the catalytic regions, or to the hydrophobic ridge interacting with Rac2.…”

Section: Role Of the Ph Domain In Plc-δ1 And Plc-β2 Activationmentioning

confidence: 99%

“…The ability of the peptide corresponding to PHβ [71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] to activate the enzyme was unexpected.…”

Section: Role Of the Ph Domain In Plc-δ1 And Plc-β2 Activationmentioning

confidence: 99%

“…Anionic lipids such as PS will increase PLC-δ1 activity [32,48] through specific interactions between PS and the C2 domain of the phospholipase [48], and interactions between the EF hands and free fatty acids also stimulate PLC-δ1 activity region [44]. Specific interactions PA and the C-terminal tail of PLC-β1 will promote its activation [83].…”

Section: Role Of the Membrane Surface In Activationmentioning

confidence: 99%

See 2 more Smart Citations

Stimulation of phospholipase Cβ by membrane interactions, interdomain movement, and G protein binding — How many ways can you activate an enzyme?

Drin

Scarlata

2007

Cellular Signalling

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Signaling proteins are usually composed of one or more conserved structural domains. These domains are usually regulatory in nature by binding to specific activators or effectors, or species that regulate cellular location, etc. Inositol-specific mammalian phospholipase C (PLC) enzymes are multidomain proteins whose activities are controlled by regulators, such as G proteins, as well as membrane interactions. One of these domains has been found to bind membranes, regulators, and activate the catalytic region. The recently solved structure of a major region of PLC-β2 together with the structure of PLC-δ1 and a wealth of biochemical studies poises the system towards an understanding of the mechanism through which their regulations occurs.

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Section: Role Of the Ph Domain In Plc-δ1 And Plc-β2 Activationmentioning

confidence: 99%

“…The ability of the peptide corresponding to PHβ [71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] to activate the enzyme was unexpected.…”

Section: Role Of the Ph Domain In Plc-δ1 And Plc-β2 Activationmentioning

confidence: 99%

Section: Role Of the Membrane Surface In Activationmentioning

confidence: 99%

See 1 more Smart Citation

Stimulation of phospholipase Cβ by membrane interactions, interdomain movement, and G protein binding — How many ways can you activate an enzyme?

Drin

Scarlata

2007

Cellular Signalling

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“…Regulation by PA required a unique PLC-β 1 PAbinding motif that mapped to a defined region within the C-terminal tail [15,34]. Neither basic nor hydrophobic residues were essential for regulation by PA. Stimulation by PA was enhanced by titration with Ca , as determined by in vitro studies using purified proteins [35].…”

Section: Synergism With Phosphatidic Acidmentioning

confidence: 99%

G protein co-signaling and challenges for translational research

Litosch

2013

Translational Neuroscience

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The Gq-linked G protein coupled receptors (GPCRs) and their signaling pathways are important clinical targets for the dementia of Alzheimer’s disease and cognitive decline with aging. Gq stimulates phospholipase C-β1 (PLC-β1) activity, increasing levels of inositol-1, 4, 5-trisphosphate (IP3) and diacylglycerol, to initiate mobilization of intracellular Ca2+ and activation of protein kinase C, respectively. While high concentrations of ligand typically evoke large sustained increases in cytosolic Ca2+ levels, it has long been appreciated that the dynamics of the Ca2+ increase are more complex and consistent with multiple levels of regulation. Physiologically relevant concentrations of Gq-ligands evoke rhythmic fluctuations or an oscillation in the level of cytosolic Ca2+. Downstream targets are tuned to respond to the frequency of the Ca2+ oscillations which in turn, reflect the oscillations in IP3 levels. Oscillatory behavior depends on the assembly of self-organizing interactions. The components that contribute to and regulate the Ca2+ oscillator have been unclear, precluding transfer of this fundamental knowledge from bench to bedside. Many GPCRs that signal with Gq also co-signal with G12. G protein co-signaling could therefore regulate the Ca2+ oscillator. This letter explores the potential relationship between Ca2+ oscillations, G protein co-signaling and cellular response in the context of our recent observations. We found that Gq efficacy is synergistic with phosphatidic acid, (PA), a signaling mediator generated downstream of activated G12 and RhoA. Regulation by PA depends on interaction with the unique PLC-β1 PA binding region. G protein co-signaling is therefore a mechanism for GPCRs to collectively assemble self-organizing interactions that regulate the Ca2+ oscillator.

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“…This technique allowed to visualize increase in lateral packing of the lipid bilayer around the receptor and changes in the receptor conformation [50]. Conformational changes induced by PA can be associated with oligomer formation and recruitment of protein to membranes leading to enzyme activation (see for instance the work of [71,72] on the phospholipase PLCb1 in mammals). Several works indicated in the past that PA and several anionic lipids such as PG can enhance MGDG synthase in plants (Fig.…”

Section: Mode Of Action Of Phosphatidic Acid In Signalling Eventsmentioning

confidence: 99%

Role of phosphatidic acid in plant galactolipid synthesis

Dubots¹,

Botté²,

Boudière³

et al. 2012

Biochimie

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Phosphatidic acid (PA) is a precursor metabolite for phosphoglycerolipids and also for galactoglycerolipids, which are essential lipids for formation of plant membranes. PA has in addition a main regulatory role in a number of developmental processes notably in the response of the plant to environmental stresses. We review here the different pools of PA dispatched at different locations in the plant cell and how these pools are modified in different growth conditions, particularly during plastid membrane biogenesis and when the plant is exposed to phosphate deprivation. We analyze how these modifications can affect galactolipid synthesis by tuning the activity of MGD1 enzyme allowing a coupling of phosphoand galactolipid metabolisms. Some mechanisms are considered to explain how physicochemical properties of PA allow this lipid to act as a central internal sensor in plant physiology.

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Structural Determinants for Phosphatidic Acid Regulation of Phospholipase C-β1

Cited by 32 publications

References 39 publications

Stimulation of phospholipase Cβ by membrane interactions, interdomain movement, and G protein binding — How many ways can you activate an enzyme?

Stimulation of phospholipase Cβ by membrane interactions, interdomain movement, and G protein binding — How many ways can you activate an enzyme?

G protein co-signaling and challenges for translational research

Role of phosphatidic acid in plant galactolipid synthesis

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