Anionic phospholipids stimulate an arachidonoyl-hydrolyzing phospholipase A2 from macrophages and reduce the calcium requirement for activity

Leslie, Christina C.; Channon, Jacqueline Y.

doi:10.1016/0005-2760(90)90129-l

Cited by 107 publications

(66 citation statements)

References 36 publications

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“…One possibility may involve formation of polyphosphoinositides. We have previously reported that phosphatidylinositol 4,5-bisphosphate activates cPLA 2 ␣ and increases its affinity for calcium (66). Phosphatidylinositol 4,5-bisphosphate also promotes binding of cPLA 2 ␣ to phospholipid vesicles and a role for the catalytic domain has been suggested (67,68).…”

Section: Discussionmentioning

confidence: 99%

Cytosolic Phospholipase A2 Translocates to Forming Phagosomes during Phagocytosis of Zymosan in Macrophages

Girotti

Evans

Burke

et al. 2004

Journal of Biological Chemistry

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Resident tissue macrophages mediate early innate immune responses to microbial infection. Cytosolic phospholipase A 2 ␣ (cPLA 2 ␣) is activated in macrophages during phagocytosis of non-opsonized yeast (zymosan) triggering arachidonic acid release and eicosanoid production. cPLA 2 ␣ translocates from cytosol to membrane in response to intracellular calcium concentration ([Ca 2؉ ] i ) increases. Enhanced green fluorescent protein (EGFP)-cPLA 2 ␣ translocated to forming phagosomes, surrounding the zymosan particle by 5 min and completely overlapping with early endosome (Rab5) and plasma membrane (F4/80) markers but only partially overlapping with resident endoplasmic reticulum proteins (GRP78 and cyclooxygenase 2). EGFP-cPLA 2 ␣ also localized to membrane ruffles during phagocytosis. Zymosan induced an initial high amplitude calcium transient that preceded particle uptake followed by a low amplitude sustained calcium increase. Both phases were required for optimal phagocytosis. Extracellular calcium chelation prevented only the sustained phase but allowed a limited number of phagocytic events, which were accompanied by translocation of cPLA 2 ␣ to the phagosome although [Ca 2؉ ] i remained at resting levels. The results demonstrate that cPLA 2 ␣ targets the phagosome membrane, which may serve as a source of arachidonic acid for eicosanoid production.

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Section: Discussionmentioning

confidence: 99%

Cytosolic Phospholipase A2 Translocates to Forming Phagosomes during Phagocytosis of Zymosan in Macrophages

Girotti

Evans

Burke

et al. 2004

Journal of Biological Chemistry

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“…Several others reports have shown that PIP n s, including PI-4,5-P 2 , enhance the activity of GIVAPLA 2 by less than 10-fold (21,22,33,55). At first glance, this seems to contradict our reports that PI-4,5-P 2 enhances the activity of GIVAPLA 2 in large unilamellar vesicles composed of PAPC by 20-fold (1 mol %) or 55-fold (3 mol %) and in PAPC/Triton X-100 mixed micelles by up to 120-fold (1 mol %) (23).…”

Section: Camentioning

confidence: 93%

“…When PI-4,5-P 2 is added to assay systems that already have high activity, the enhancing effects of PI-4,5-P 2 may appear muted as in Lyso-PC micelles (Fig. 9B) and small unilamellar vesicles (21,22,33,55). Nevertheless, despite the high basal levels of activity seen in these reported assays, the additions of small amounts of PI-4,5-P 2 led to reliable, although modest, 4 -6-fold activity enhancements as in Fig.…”

Section: Camentioning

confidence: 99%

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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“…The Ca 2ϩ -independent localization of cPLA 2 a on the perinuclear membranes may be regulated by phosphorylation, anionic lipids, and hydrophobic binding of the catalytic domain, as described below. 15,45,[49][50][51] 3-3. Regulation by Phosphorylation In most agonist/cell systems, activation of cPLA 2 a is regulated by phosphorylation in addition to a rise in intracellular Ca 2ϩ concentration.…”

Section: ؉mentioning

confidence: 99%

Regulatory Mechanism and Physiological Role of Cytosolic Phospholipase A2

Hirabayashi

Murayama

Shimizu

2004

Biological & Pharmaceutical Bulletin

216

184

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Cytosolic phospholipase A 2 a a (cPLA 2 a a) preferentially hydrolyzes phospholipids containing arachidonic acid and plays a key role in the biosynthesis of eicosanoids. This review discusses the essential features of cPLA 2 a a regulation and addresses new insights into the functional properties of this enzyme. Full activation of the enzyme requires Ca 2؉ binding to an N-terminal C2 domain and phosphorylation on serine residues. Ca 2؉ binding induces translocation of cPLA 2 a a from the cytosol to the perinuclear membranes. Serine phosphorylation is mediated by mitogen-activated protein kinases (MAPKs), Ca 2؉ /calmodulin-dependent protein kinase II, and MAPK-interacting kinase Mnk1. Interaction with proteins and lipids, which include vimentin, annexins, NADPH oxidase, phosphatidylcholine, phosphatidylinositol 4,5-bisphosphate (PIP 2 ), and ceramide-1-phosphate, can also modulate the activity of cPLA 2 a a. Recent evidence has established the physiological and pathological roles of cPLA 2 a a using cPLA 2 a a knockout mice. This enzyme has been implicated in fertility, striated muscle growth, renal concentration, postischemic brain injury, arthritis, inflammatory bone resorption, intestinal polyposis, pulmonary fibrosis, acute respiratory distress syndrome, and autoimmune encephalomyelitis. Now novel three paralogs, cPLA 2 b b, cPLA 2 g g, and cPLA 2 d d, have been identified in humans. cPLA 2 g g is distinct from others in that it is farnesylated and lacks the C2 domain. Biological roles for these new enzymes have not yet been defined.

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Anionic phospholipids stimulate an arachidonoyl-hydrolyzing phospholipase A2 from macrophages and reduce the calcium requirement for activity

Cited by 107 publications

References 36 publications

Cytosolic Phospholipase A2 Translocates to Forming Phagosomes during Phagocytosis of Zymosan in Macrophages

Cytosolic Phospholipase A2 Translocates to Forming Phagosomes during Phagocytosis of Zymosan in Macrophages

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

Regulatory Mechanism and Physiological Role of Cytosolic Phospholipase A2

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