Role of phospholipase D1 in glucose-induced insulin secretion in pancreatic β cells

Wei, Na; Park, Shin Young; Han, Joong‐Soo

doi:10.3858/emm.2010.42.6.047

Cited by 25 publications

(20 citation statements)

References 39 publications

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“…We also demonstrated that H-Ras-induced PLD activity was dependent on ARF6 (40). ARF6 has also been implicated in the glucose stimulation of insulin secretion (19), indicating that ARF6 is activated in response to nutrients. Thus, the involvement of RalA, in the amino acid-and glucose-dependent PLD activity shown in Fig.…”

Section: Pld Activity In Human Cancer Cells Is Dependent On Aminomentioning

confidence: 62%

“…Our data are consistent with this model in that there is agreement that Rheb is critical for the activation of mTORC1 in response to amino acids. However, our study also takes into account previous studies linking the nutrient response of mTORC1 to RalA (12), ARF6 (19), and hVps34 (22)(23)(24)(25). A common denominator for all three of these factors is PLD and a direct link to mTORC1 through PA.…”

Section: Discussionmentioning

confidence: 99%

“…these GTPases have been implicated in both response to nutrients (12,19,43) and stimulation of PLD activity (13,14,18,40). RalA is constitutively associated with PLD1 but does not activate PLD1 by itself.…”

Section: Discussionmentioning

confidence: 99%

“…Although RalA does not activate PLD1 directly, it stimulates the association of PLD1 with ADP-ribosylation factor (ARF) family GTPases, which do increase the activity of PLD1 (18). Significantly, ARF6 has been implicated in the response of mTORC1 to glucose (19). An important recent study also linked Rheb and PLD1.…”

mentioning

confidence: 99%

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Phospholipase D Mediates Nutrient Input to Mammalian Target of Rapamycin Complex 1 (mTORC1)

Salloum

Medlin

et al. 2011

Journal of Biological Chemistry

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The mammalian target of rapamycin (mTOR) is a critical sensor of nutritional sufficiency. Although much is known about the regulation of mTOR in response to growth factors, much less is known about the regulation of mTOR in response to nutrients. Amino acids have no impact on the signals that regulate Rheb, a GTPase required for the activation of mTOR complex 1 (mTORC1). Phospholipase D (PLD) generates a metabolite, phosphatidic acid, that facilitates association between mTOR and the mTORC1 co-factor Raptor. We report here that elevated PLD activity in human cancer cells is dependent on both amino acids and glucose and that amino acid-and glucose-induced increases in mTORC1 activity are dependent on PLD. Amino acid-and glucose-induced PLD and mTORC1 activity were also dependent on the GTPases RalA and ARF6 and the type III phosphatidylinositol-3-kinase hVps34. Thus, a key stimulatory event for mTORC1 activation in response to nutrients is the generation of phosphatidic acid by PLD.The mammalian target of rapamycin (mTOR) 2 is a critical regulator of cell growth and cell cycle progression. mTOR is activated in response to both growth factors and nutrients (1). mTOR exists as two complexes, mTORC1 and mTORC2. Although both mTORC1 and mTORC2 are responsive to growth factors, mTORC1 is believed to be the primary sensor of nutrient and energy sufficiency (2-4). mTORC1 is activated in response to insulin and other peptide hormones that activate type I phosphatidylinositol (PI) 3-kinases (PI3Ks) that generate PI 3,4,5-trisphosphate. The activation of mTORC1 via PI3K involves the Akt-mediated suppression of the tuberous sclerosis complex (TSC), which consists of TSC1 and TSC2. TSC1/2 functions as a GTPase-activating protein for Rheb (Ras homologue enriched in brain), a GTPase that directly interacts with and contributes to the activation of mTORC1 (2). Although Rheb is required for the amino acid stimulation of mTORC1, starving cells of amino acids has no effect on GTP loading (4 -7). In addition, amino acid starvation was still able to suppress mTORC1 in cells lacking the Rheb GTPase-activating complex protein TSC2 (4 -7). Therefore, although there is a requirement for GTP-bound Rheb for induction of mTORC1 by amino acids, amino acids do not impact on Rheb activity, indicating that regulation of Rheb does not stimulate mTORC1 in response to amino acids.It was recently reported that Rag GTPases are critical for targeting mTORC1 to lysosomal compartments in response to amino acids (8 -10), and a model was proposed whereby the targeting of mTOR to lysosomal membranes containing GTPbound Rheb was sufficient to activate mTORC1 (10, 11). However, several other factors implicated in the regulation of mTORC1 in response to amino acids were not accounted for in this model. The Ras family GTPase RalA was reported to be required for amino acid induction of mTORC1 (12). Significantly, RalA is constitutively associated with phospholipase D1 (PLD1) (13,14). PLD1 generates the lipid second messenger phosphatidic acid (PA), which is r...

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Section: Pld Activity In Human Cancer Cells Is Dependent On Aminomentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Phospholipase D Mediates Nutrient Input to Mammalian Target of Rapamycin Complex 1 (mTORC1)

Salloum

Medlin

et al. 2011

Journal of Biological Chemistry

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“…The translocation of ARF6 stimulates PLD1 [113] and PLD2 [108] in vivo. The importance of ARF protein exemplified by ARF1 is proved by its necessity for the activation of PLDs.…”

Section: +mentioning

confidence: 99%

Molecular structure of phospholipase D and regulatory mechanisms of its activity in plant and animal cells

Kolesnikov

Nokhrina

Kretynin

et al. 2012

Biochemistry Moscow

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Abbreviations: Gα, α-subunit of heterotrimeric G-protein; PKC, protein kinase C; PLD, phospholipase D; PtdIns(4,5)P 2 , phosphatidylinositol-4,5-bisphosphate. * To whom correspondence should be addressed.Abstract⎯Phospholipase D (PLD) catalyzes hydrolysis of phospholipids with production of phosphatidic acids, which often act as secondary messengers on transmission of intracellular signals. This review summarizes data of various leading laboratories on specific features of organization and regulation of PLD activity in plant and animal cells. The main structural domains of PLD (C2, PX, PH), the active site, and other functionally important parts of the enzyme are considered. Regulatory mechanisms of PLD activity are characterized in detail. Studies associated with molecular design, analysis, and synthesis of new nontoxic substances capable of inhibiting different PLD isoenzymes in vivo are shown to be promising for biotechnology and medicine.

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Phosphatidic Acid-Mediated Signaling

Liu

Wang

2013

Advances in Experimental Medicine and Biology

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Phosphatidic acid (PA) is recognized as an important class of lipid messengers. The cellular PA levels are dynamic; PA is produced and metabolized by several enzymatic reactions, including different phospholipases, lipid kinases, and phosphatases. PA interacts with various proteins and the interactions may modulate enzyme catalytic activities and/or tether proteins to membranes. The PA-protein interactions are impacted by changes in cellular pH and other effectors, such as cations. PA is involved in a wide range of cellular processes, including vesicular trafficking, cytoskeletal organization, secretion, cell proliferation, and survival. Manipulations of different PA production reactions alter cellular and organismal response to a wide range of abiotic and biotic stresses. Further investigations of PA's function and mechanisms of action will advance not only the understanding of cell signaling networks but also may lead to biotechnological and pharmacological applications.

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Role of phospholipase D1 in glucose-induced insulin secretion in pancreatic β cells

Cited by 25 publications

References 39 publications

Phospholipase D Mediates Nutrient Input to Mammalian Target of Rapamycin Complex 1 (mTORC1)

Phospholipase D Mediates Nutrient Input to Mammalian Target of Rapamycin Complex 1 (mTORC1)

Molecular structure of phospholipase D and regulatory mechanisms of its activity in plant and animal cells

Phosphatidic Acid-Mediated Signaling

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