Phosphorylation of Cytosolic Group IV Phospholipase A2 Is Necessary but Not Sufficient for Arachidonic Acid Release in P388D1 Macrophages

Balboa, Marı́a A.; Balsinde, Jesús; Dennis, Edward A.

doi:10.1006/bbrc.1999.1964

Cited by 29 publications

(28 citation statements)

References 32 publications

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“…In the presence of PI-4,5-P 2 and the absence of Ca 2ϩ , GIVAPLA 2 both bound to phosphatidylcholine-containing surfaces and was active in vitro (23). Extending this work to cellular systems, we demonstrated that elevated levels of both phosphatidylinositol 4-phosphate (PI-4-P) and PI-4,5-P 2 correlated with and were necessary for GIVAPLA 2 -dependent arachidonate release by lipopolysaccharide-primed, UV lightactivated P388D 1 murine macrophage-like cells (24,25). Importantly, no change in intracellular [Ca 2ϩ ] was detected, further supporting the potential importance of the PIP n effect (24).…”

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confidence: 75%

Essential Ca2+-independent Role of the Group IVA Cytosolic Phospholipase A2 C2 Domain for Interfacial Activity

Six¹,

Dennis

2003

Journal of Biological Chemistry

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mentioning

confidence: 75%

Essential Ca2+-independent Role of the Group IVA Cytosolic Phospholipase A2 C2 Domain for Interfacial Activity

Six¹,

Dennis

2003

Journal of Biological Chemistry

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“…For example, during IgG-mediated phagocytosis by human monocytes, activation of DAG-dependent forms of protein kinase C precedes AA release (65). If protein kinase C or related kinases mediate the DAG effect on cPLA 2 a, this would probably be an indirect effect, for example, via the MAPK pathway (66)(67)(68). In this regard, we have recently described the JNK-dependent phosphorylation activation of cPLA 2 a in human monocytederived macrophages (39).…”

Section: Discussionmentioning

confidence: 99%

Subcellular Localization and Role of Lipin-1 in Human Macrophages

Valdearcos

Esquinas²,

Meana³

et al. 2011

The Journal of Immunology

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The lipins have been described as metabolic enzymes that regulate lipid biosynthesis and also signaling processes by controlling the cellular concentration of bioactive lipids, phosphatidic acid, and diacylgycerol. In the present work we have studied the subcellular localization and role of lipin-1 in human monocyte-derived macrophages. Human macrophages express lipin-1 isoforms α and β. A transfected lipin-1α–enhanced GFP construct associates with membranes of cellular organelles that can be stained with Nile Red. Colocalization experiments with lipid droplet (LD)-specific proteins such as adipophilin/adipose differentiation-related protein/perilipin 2 or TIP47/perilipin 3 show that both proteins colocalize with lipin-1α in the same cellular structures. Reduction of the expression levels of lipin-1 by small interfering RNA technology does not impair triacylglycerol biosynthesis but reduces the size of LDs formed in response to oleic acid. In agreement with these data, peritoneal macrophages from animals that carry a mutation in the Lpin-1 gene (fld animals) also produce less and smaller LDs in response to oleic acid. Mass spectrometry determinations demonstrate that the fatty acid composition of triacylglycerol in isolated LDs from lipin-1–deficient cells differs from that of control cells. Moreover, activation of cytosolic group IVA phospholipase A2α, a proinflammatory enzyme that is also involved in LD biogenesis, is also compromised in lipin-1–deficient cells. Collectively, these data suggest that lipin-1 associates with LDs and regulates the activation of cytosolic group IVA phospholipase A2α in human monocyte-derived macrophages.

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“…Depending on cell type and/or stimulus, various members of the MAPK family may catalyze cPLA 2 phosphorylation (8,42). In the P388D 1 macrophage-like cell system we previously showed that phosphorylation of cPLA 2 at Ser 505 occurs during stimulation of the cells via TLR4, and that this phosphorylation is mediated by the ERKs p42 (ERK1) and p44 (ERK2) (43). We demonstrate in this work that inhibition of sPLA 2 -V expression and activity by either siRNA or chemical inhibitors results in reduced phosphorylation of the ERKs and cPLA 2 in response to some but not all TLRs.…”

Section: Discussionmentioning

confidence: 99%

“…Many of the data currently available in the literature suggest that cPLA 2 is phosphorylated and activated by either the ERK1/2 (p44/p42) or p38 isoforms of MAPK; the activation mechanism may vary with the cell type and activation regimen (42). In this regard, we have previously shown that phosphorylation activation of the AA-releasing cPLA 2 at Ser 505 occurs during stimulation of P388D 1 macrophage-like cells by various agonists, including the TLR4 agonist LPS, and that this phosphorylation is effected by the ERKs p42 (ERK1) and p44 (ERK2) (43,44). Fig.…”

Section: Spla 2 Modulates Erk and Cpla 2 Phosphorylation During Stimumentioning

confidence: 99%

Coordinate Regulation of TLR-Mediated Arachidonic Acid Mobilization in Macrophages by Group IVA and Group V Phospholipase A2s

Ruipérez

Astudillo²,

Balboa³

et al. 2009

The Journal of Immunology

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Macrophages can be activated through TLRs for a variety of innate immune responses. In contrast with the wealth of data existing on TLR-dependent gene expression and resultant cytokine production, very little is known on the mechanisms governing TLR-mediated arachidonic acid (AA) mobilization and subsequent eicosanoid production. We have previously reported the involvement of both cytosolic group IVA phospholipase A2 (cPLA2) and secreted group V phospholipase A2 (sPLA2-V) in regulating the AA mobilization response of macrophages exposed to bacterial LPS, a TLR4 agonist. In the present study, we have used multiple TLR agonists to define the role of various PLA2s in macrophage AA release via TLRs. Activation of P388D1 and RAW2647.1 macrophage-like cells via TLR1/2, TLR2, TLR3, TLR4, TLR6/2, and TLR7, but not TLR5 or TLR9, resulted in AA mobilization that appears to involve the activation of both cPLA2 and sPLA2 but not of calcium-independent phospholipase A2. Furthermore, inhibition of sPLA2-V by RNA interference or by two cell-permeable compounds, namely scalaradial and manoalide, resulted in a marked reduction of the phosphorylation of ERK1/2 and cPLA2 via TLR1/2, TLR2, TLR3, and TLR4, leading to attenuated AA mobilization. Collectively, the results suggest a model whereby sPLA2-V contributes to the macrophage AA mobilization response via various TLRs by amplifying cPLA2 activation through the ERK1/2 phosphorylation cascade.

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Phosphorylation of Cytosolic Group IV Phospholipase A2 Is Necessary but Not Sufficient for Arachidonic Acid Release in P388D1 Macrophages

Cited by 29 publications

References 32 publications

Essential Ca2+-independent Role of the Group IVA Cytosolic Phospholipase A2 C2 Domain for Interfacial Activity

Essential Ca2+-independent Role of the Group IVA Cytosolic Phospholipase A2 C2 Domain for Interfacial Activity

Subcellular Localization and Role of Lipin-1 in Human Macrophages

Coordinate Regulation of TLR-Mediated Arachidonic Acid Mobilization in Macrophages by Group IVA and Group V Phospholipase A2s

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