Regulation of interleukin‐2 responses by phosphatidic acid

Cano, Eva; Muñoz‐Fernández, María Ángeles; Fresno, Manuel

doi:10.1002/eji.1830220731

Cited by 26 publications

(12 citation statements)

References 49 publications

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“…In both highly metabolically labeled cells and cell extracts, no PLD activity was observed at the times when the late IL-2stimulated PA accumulation occurred. In addition, no acute IL-2 stimulation of PLD in CTLL-2 cells was observed which was in disagreement with the observations by Cano and coworkers [28]. Using NIH3T3 ¢broblasts as a positive control, PMA, the activator of classical isoforms of PKC, was able to increase PLD activity.…”

Section: Discussioncontrasting

confidence: 63%

Interleukin‐2 stimulates a late increase in phosphatidic acid production in the absence of phospholipase D activation

et al. 1998

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The signal transduction pathways involving phospholipid metabolism during T-cell proliferation remain partly undefined. Herein we show that interleukin-2 caused a late ( s 12 h) rise in the intracellular phosphatidic acid content of CTLL-2 cells which was a consequence of the activation of the enzyme diacylglycerol kinase. No activation of phospholipase D was observed at similar times. Incubation of the cells with a recognized diacylglycerol kinase K K isoform inhibitor, R59499, prior to interleukin-2 stimulation was able to block cell cycle entry, diacyglycerol kinase activation and phosphatidic acid accumulation. In contrast, when R59499 was added 3 h after interleukin-2, few or no observable effects on the above three parameters were noticed. These results suggest that the early signaling employed by IL-2 involving the K K isoform of diacylglycerol kinase is sufficient to control the late increase in phosphatidic acid and that phosphatidic acid is a mitogenic agent in T-cells.z 1998 Federation of European Biochemical Societies.

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Section: Discussioncontrasting

confidence: 63%

Interleukin‐2 stimulates a late increase in phosphatidic acid production in the absence of phospholipase D activation

et al. 1998

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“…In response to mitogenic stimulation, PA levels quickly rise and fall back toward basal levels within 1 hour of stimulation (Cano et al, 1992; Fang et al, 2001; Fukami and Takenawa, 1992). Given this transient PA presence, we wondered if DEPTOR re-associated with mTORC1 over time.…”

Section: Resultsmentioning

confidence: 99%

Rapid Mitogenic Regulation of the mTORC1 Inhibitor, DEPTOR, by Phosphatidic Acid

Yoon

Rosenberger

et al. 2015

Molecular Cell

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SUMMARY The mammalian target of rapamycin complex 1 (mTORC1) is regulated, in part, by the endogenous inhibitor DEPTOR. However, the mechanism of DEPTOR regulation with regard to rapid mTORC1 activation remains unknown. We report that DEPTOR is rapidly and temporarily dissociated from mTORC1 upon mitogenic stimulation, suggesting a mechanism underlying acute mTORC1 activation. This mitogen-stimulated DEPTOR dissociation is blocked by inhibition or depletion of the mTORC1 regulator, phospholipase D (PLD), and recapitulated with the addition of the PLD product phosphatidic acid (PA). Our mass spectrometry analysis has independently identified DEPTOR as an mTOR binding partner dissociated by PA. Interestingly, only PA species with unsaturated fatty acid chains, such as those produced by PLD, are capable of displacing DEPTOR and activating mTORC1, with high affinity for the FRB domain of mTOR. Our findings reveal a novel mechanism of mTOR regulation and provide a molecular explanation for the exquisite specificity of PA function.

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“…PLD is frequently activated together with or downstream from PLC (Liscovitch, 1992). Both tyrosine kinase receptors and G protein-coupled receptors have been shown to activate PLC and PLD (Billah and Anthes, 1990;Exton, 1990Exton, , 1994Exton et al, 1991;Xie and Dubyak, 1991;Bourgoin and Grinstein, 1992;Cano et al, 1992;Dings et al, 1992;Jiang et al, 1994).…”

Section: Activation Of Pldmentioning

confidence: 99%

G Protein Activation Stimulates Phospholipase D Signaling in Plants.

et al. 1995

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We provide direct evidence for phospholipase D (PLD) signaling i n plants by showing that this enzyme is stimulated by the G protein activators mastoparan, ethanol, and cholera toxin. An i n vivo assay for PLD activity i n plant cells was developed based on the use of a "reporter alcohol" rather than water as a transphosphatidylation substrate. The product was a phosphatidyl alcohol, which, in contrast to the normal product phosphatidic acid, i s a specific measure of PLD activity.When 32P-labeled cells were treated with 0.1% n-butanol, 3*P-phosphatidyl butanol (32P-PtdBut) was formed in a timedependent manner. In cells treated with any of the three G protein activators, the production of 32P-PtdBut was increased i n a dose-dependent manner. The G protein involved was pertussis toxin insensitive. Ethanol could activate PLD but was itself consumed by PLD as transphosphatidylation substrate. In contrast, secondary alcohols (e.g., sec-butyl alcohol) activated PLD but did not function as substrate, whereas tertiary alcohols did neither. Although most of the experiments were performed with the green alga Chlamydomonas eugametos, the relevance for higher plants was demonstrated by showing that PLD in carnation petals could also be activated by mastoparan. The results indicate that PLD activation must be considered as a potential signal transduction mechanism in plants, just as in animals.

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Regulation of interleukin‐2 responses by phosphatidic acid

Cited by 26 publications

References 49 publications

Interleukin‐2 stimulates a late increase in phosphatidic acid production in the absence of phospholipase D activation

Interleukin‐2 stimulates a late increase in phosphatidic acid production in the absence of phospholipase D activation

Rapid Mitogenic Regulation of the mTORC1 Inhibitor, DEPTOR, by Phosphatidic Acid

G Protein Activation Stimulates Phospholipase D Signaling in Plants.

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