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1 n of the calcium-dependent phospholipase A2 (cPLA2).
2 he activation of group IVA phospholipase A2 (cPLA2).
3 tion of group IV cytosolic phospholipase A2 (cPLA2).
4 gs of the 85-kDa cytosolic phospholipase A2 (cPLA2).
5 n also activated cytosolic phospholipase A2 (cPLA2).
6 phospholipids by cytosolic phospholipase A2 (cPLA2).
7 tes and this is necessary for stimulation of cPLA2.
8 sphatidylcholine vesicle binding affinity of cPLA2.
9 e cells with fluorescent protein chimeras of cPLA2.
10 on of other annexins as well as of COX-2 and cPLA2.
11 th the dexamethasone-mediated suppression of cPLA2.
12 h accompanied enhanced catalytic activity of cPLA2.
13 ynthesis, but not for the phosphorylation of cPLA2.
14 mediated by calcium-triggered activation of cPLA2.
15 e believe is a novel inherited deficiency of cPLA2.
16 apillaries from male and female mice lacking cPLA2.
17 terfering with the intracellular movement of cPLA2.
22 FB mediate hypoxia-induced Src-PLD1-PKCgamma-cPLA2 activation and retinal neovascularization via acti
27 derstand the mechanisms of Src-PLD1-PKCgamma-cPLA2 activation by vascular endothelial growth factor A
29 sessments were used to test whether blocking cPLA2 activation pharmacologically or genetically reduce
30 ctively, the results suggest a model whereby cPLA2 activation regulates Group V sPLA2 expression, whi
33 upport the hypothesis that glutamate signals cPLA2 activation, resulting in overexpression of blood-b
34 a2+ availability is a dispensable signal for cPLA2 activation, which suggests the existence of altern
42 PLA2 to BMMC caused a transient increase in cPLA2 activity and translocation of this activity to mem
44 of the 16:4(n-3)-GPR120 axis led to enhanced cPLA2 activity in these splenic macrophages and secretio
48 residence is important in the regulation of cPLA2 activity, we explored the contributions of the C2
51 d an increase in cytosolic phospholipase A2 (cPLA2) activity with a preferential release of membrane-
52 ibited tumor cell growth, phosphorylation of cPLA2 alpha promoted growth and counteracted Smad-mediat
53 expression of cPLA2alpha, but inhibition of cPLA2 alpha, cyclooxygenase-2 (COX-2), or EP1 receptor r
54 ies the action of cytosolic phospholipase A2(cPLA2) alpha in regulating eicosanoid biosynthesis by mo
55 pase A2, and the cytosolic phospholipase A2 (cPLA2)alpha isoform has been specifically shown to direc
58 rs at micromolar Ca2+ concentrations for the cPLA2-alpha C2 domain, but requires 3- and 10-fold highe
61 ctively, require greater than 400 ms for the cPLA2-alpha domain, compared to 13 ms for the PKC-beta d
63 LA2-beta, that has significant homology with cPLA2-alpha in both the calcium-dependent lipid binding
65 A-AM demonstrated that a substantial pool of cPLA2-alpha remained associated with membrane fractions
66 timulation with calcium-mobilizing agonists, cPLA2-alpha translocates to intracellular phospholipid m
67 Calcium-independent membrane association of cPLA2-alpha was not due to hydrophobic or cytoskeletal i
68 is study, the calcium-induced association of cPLA2-alpha with EA.hy.926 endothelial cell membranes wa
70 proteins: cytosolic phospholipase A2-alpha (cPLA2-alpha), protein kinase C-beta (PKC-beta), and syna
71 s the generation of free arachidonic acid by cPLA2-alpha, this enzyme has become an attractive pharma
74 estigate whether cytosolic phospholipase A2 (cPLA2 ), an important isoform of PLA2 that mediates the
75 inated regulation of two metabolic pathways (cPLA2 and 5-lipoxygenase), which results in the generati
78 genes that govern the lipoxygenase pathway, cPLA2 and 5-LOX, was observed in rats following inoculat
81 for 18 h, i.e., a lag in phosphorylation of cPLA2 and ERK1/2 lasting 30 s before its eventual rise.
83 te a change in the intracellular position of cPLA2 and found that cPLA2 did not translocate normally
85 ExoU interacts in vitro with an inhibitor of cPLA2 and iPLA2 enzymes and contains a putative serine-a
87 cytosolic and the calcium-independent PLA2s (cPLA2 and iPLA2), are key enzymes mediating oligomeric a
88 ds and putative membrane-binding residues of cPLA2 and measured the effects of mutations on its enzym
90 this study we investigated the influence of cPLA2 and secreted phospholipase A2 (sPLA2) Group IIA, G
91 d5 is accompanied by the rapid activation of cPLA2 and the cPLA2-dependent release of [3H]arachidonic
93 on of both chlamydial activation of the host cPLA2 and uptake of glycerophospholipids from the host c
94 blocked by various inhibitors of cytosolic (cPLA2) and Ca2+ -independent (iPLA2) phospholipase A2 en
95 osphorylation of cytosolic phospholipase A2 (cPLA2) and consequent thromboxane A2 (TXA2) production.
97 the kinetics of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK1/2
98 the function of cytosolic phospholipase A2 (cPLA2) and its role in membrane regulation at the Golgi
99 osphorylation of cytosolic phospholipase A2 (cPLA2), and arachidonic acid (AA) and LTC4 release follo
101 itor of cPLA2, short interfering RNA against cPLA2, and several calcium signaling blockers, indicatin
102 ted in increased interaction between p11 and cPLA2, anti-cPLA2 antibodies were used to immunoprecipit
103 ased interaction between p11 and cPLA2, anti-cPLA2 antibodies were used to immunoprecipitate p11.cPLA
104 ere activated by an autocrine loop involving cPLA2, arachidonic acid release, COX-2-dependent PGI(2)
105 ines, IL-1beta and IL-6, thereby identifying cPLA2 as an important regulator of the inflammatory prog
106 It was over 70 times more selective for the cPLA2 as compared with the human nonpancreatic secreted
107 atic activity of cytosolic phospholipase A2 (cPLA2) as at-tested to by arachidonic acid release withi
108 thiol antioxidant NAC reduces activation of cPLA2 (assessed by isoform gel-shift and membrane transl
110 report the X-ray crystal structure of human cPLA2 at 2.5 A. cPLA2 consists of an N-terminal calcium-
111 ms of cPLA2, we show that phosphorylation of cPLA2 at both Ser-505 and Ser-727 and elevation of Ca(2+
112 blocked collagen-induced phosphorylation of cPLA2 at its two phosphorylation sites in vivo, Ser505 a
119 cDNA encoding a 1012-amino acid polypeptide cPLA2-beta, that has significant homology with cPLA2-alp
121 g surface on the Ca2+-activated C2 domain of cPLA2 by engineering a single cysteine substitution at 1
123 swelling of cells and their nuclei activates cPla2 by translocating it from the nucleoplasm to the nu
125 beta-sandwich region is found; however, the cPLA2 C2 domain is translocated 5-7 A deeper into the me
126 ing the high-resolution crystal structure of cPLA2-C2 as a starting point, we embedded two copies of
127 the C2 domain of cytosolic phospholipase A2 (cPLA2-C2) in a 1-palmitoyl-2-oleoyl-phosphatidylcholine
128 These results demonstrate a role for the cPLA2 catalytic domain in regulating membrane associatio
131 ntibodies were used to immunoprecipitate p11.cPLA2 complexes and Western blots of the immunoprecipita
132 y crystal structure of human cPLA2 at 2.5 A. cPLA2 consists of an N-terminal calcium-dependent lipid-
133 s that host cell cytosolic phospholipase A2 (cPLA2) contributes to E. coli K1 invasion of BMECs but n
136 and activity of cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and production of PGs.
137 eover small inhibitory RNAs directed against cPLA2 decreased the effect of A23187 and EGF on IL-8 and
138 d activation of eosinophils derived from the cPLA2-deficient mouse corroborated that hVPLA2 mediates
139 rachidonic acid release and translocation of cPLA2, demonstrating the requirement for a functional C2
141 ied by the rapid activation of cPLA2 and the cPLA2-dependent release of [3H]arachidonic acid ([3H]AA)
142 tracellular position of cPLA2 and found that cPLA2 did not translocate normally in infected cells, ra
143 ined the role of cytosolic phospholipase A2 (cPLA2) during human eosinophil adherence to ICAM-1- or V
146 dentify protein residues in the C2 domain of cPLA2 essential for its Ca2+ and membrane binding, we se
147 ound to be the most potent inhibitor of GIVA cPLA2, exhibiting an XI(50) value of 0.011 mole fraction
151 uation were used to access expression of the cPLA2 gene in rat small intestinal epithelial and mouse
154 ich the gene for cytosolic phospholipase A2 (cPLA2) has been disrupted to demonstrate the absolute re
157 ly IL-3 priming results from preconditioning cPLA2, i.e., causing its phosphorylation, while late pri
158 c Abeta(1-42) to increase phosphorylation of cPLA2 in astrocytes through the NADPH oxidase and mitoge
159 to demonstrate the absolute requirement for cPLA2 in both the immediate and the delayed phases of ei
160 0 minutes postinjury or genetically deleting cPLA2 in mice ameliorated motor deficits, and reduced ce
162 However, no studies addressed the role of cPLA2 in the regulation of cholesterol-rich membranes th
165 kinases MNK1, MSK1, and PRAK1 phosphorylate cPLA2 in vitro uniquely on Ser-727 as shown by mass spec
166 s were able to phosphorylate wild-type human cPLA2 in vitro, although to different extents, but not c
168 nd activation of cytosolic phospholipase A2 (cPLA2) in intact cells remain to be fully characterized.
172 ts on the membrane binding and activation of cPLA2, indicating that two calcium ions bound to the C2
173 accompanied by a time-dependent gel shift of cPLA2 induced by phosphorylation of cPLA2 at various sit
176 ion of arachidonic acid to eosinophils after cPLA2 inhibition with arachidonyl trifluoromethylketone
178 eatment with the most potent 2-oxoester GIVA cPLA2 inhibitor resulted in over 50% decrease in KLA-eli
179 chidonyl trifluoromethyl ketone, a selective cPLA2 inhibitor, and was confirmed with BMEC derived fro
183 donic acid release are abrogated by group IV cPLA2 inhibitors (methyl arachidonyl fluorophosphate and
184 up leads to highly potent and selective GIVA cPLA2 inhibitors (X I(50) values 0.00007-0.00008) and do
185 roup IV cPLA2, to infected MPhi treated with cPLA2 inhibitors completely restored the antimycobacteri
186 ion of GV sPLA2, and none of the potent GIVA cPLA2 inhibitors inhibited either GV sPLA2 or GVIA iPLA2
188 The novel, highly potent and selective GIVA cPLA2 inhibitors provide excellent tools for the study o
194 ding loops show that the membrane binding of cPLA2 is largely driven by hydrophobic interactions resu
195 y, while the FMLP-induced phosphorylation of cPLA2 is not affected by the inhibitors of the p38 MAP k
197 iPLA2 is the dominant PLA2 in rat brain, and cPLA2 is the most abundant PLA2 in P388D1 macrophages an
198 both NIH3T3 and MC3T3E1 cells suggests that cPLA2 is the most likely enzyme that catalyzes the relea
201 e Group IVA cytosolic phospholipase A2 (GIVA cPLA2) is a key provider of substrates for the productio
203 previously that cytosolic phospholipase A2 (cPLA2) is able to activate gene expression through PPAR-
204 man platelets, cytosolic phospholipase A(2) (cPLA2) is phosphorylated on Ser-505 by p38 protein kinas
205 riments show that cytosolic phospholipase 2 (cPLA2) is the key enzyme mediating the p25-induced LPC p
207 Group IVA cytosolic phospholipase A2 (GIVA cPLA2) is the rate-limiting provider of pro-inflammatory
208 that sPLA2 isoforms (pla2g5, 12a, and 12b), cPLA2 isoform (pla2g4a), iPLA2 isoform (pla2g6), and PLA
209 l migration in vitro Genetic ablation of the cPLA2 isoform cPLA2alpha dramatically reduced lung infla
210 gamma interferon, or their combination, and cPLA2-IVA mediated the release of arachidonic acid, whic
212 marrow-derived macrophages (BMDMs) expressed cPLA2-IVA, cPLA2-IVB, iPLA2-VI, sPLA2-IIE, and sPLA2-XII
220 rophages to UV radiation results in a rapid, cPLA2-mediated arachidonic acid mobilization, without in
225 COX-2 of its substrate by the suppression of cPLA2 mRNA expression is an additional mechanism used by
229 l pretreatment with AACOCF3 (an inhibitor of cPLA2), nifedipine (a Ca(2+) channel blocker), or 3'-met
233 ntigen, it had no effect on translocation of cPLA2 or ERK1/2 activation, suggesting that it does not
234 in the level of cytosolic phospholipase A2 (cPLA2) or COX-1 were observed, and Group IIA sPLA2 was n
235 ands' cycle by knockdown of phospholipase 2 (cPLA2) or overexpression of lysophosphatidycholine acylt
242 H, caused complete inhibition of ADP-induced cPLA2 phosphorylation and TXA2 generation, without affec
244 cal inhibition of p38 leads to inhibition of cPLA2 phosphorylation at both Ser-505 and Ser-727 sugges
247 dhesion to VCAM-1 corresponded temporally to cPLA2 phosphorylation, which accompanied enhanced cataly
250 e in intracellular calcium concentration nor cPLA2 phosphorylation; consequently, cPLA2 activity was
251 enase pathway showed that gene disruption of cPLA2 prevented the provision of arachidonic acid substr
254 ncorporated similar levels of phosphate into cPLA2 relative to the ability of each kinase to stimulat
255 damage activates cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (AA), which is oxidiz
257 action of iPLA2 is immediate, the action of cPLA2 requires a lag time of approximately 12-15 min, pr
258 ACOCF3) and ShRNA mediated downregulation of cPLA2 resulted in reduced LDs, and increased autophagy.
260 ff assays showed a marked decline in de novo cPLA2 RNA synthesis, implicating a transcriptional mecha
263 l fluorophosphonate, a specific inhibitor of cPLA2, short interfering RNA against cPLA2, and several
264 port that activation of the host Raf-MEK-ERK-cPLA2 signaling cascade is required for the chlamydial u
265 be the major modulator of Src-PLD1-PKCgamma-cPLA2 signaling in HRMVECs, facilitating their angiogeni
267 ceptors 1 and 4, cytosolic phospholipase A2 (cPLA2), Src tyrosine kinases, p38 MAPK, phospholipase C,
271 ible for the subsequent induction of type IV cPLA2 that mediates the release of arachidonic acid for
272 nts a novel structural class of inhibitor of cPLA2 that partitions into the phospholipid bilayer and
274 isphosphate (PtdInsP2) in the association of cPLA2 to model membranes and hence in the regulation of
275 hought to be needed for translocation of the cPLA2 to the membrane via a C2 domain, whereas the role
277 ecessary and sufficient for translocation of cPLA2 to the nuclear envelope when calcium is increased;
279 est and negligible effects on the binding of cPLA2 to zwitterionic and anionic membranes, respectivel
280 Translocation of cytosolic phospholipase A2 (cPLA2) to Golgi and ER in response to intracellular calc
281 chidonic acid, the major product of group IV cPLA2, to infected MPhi treated with cPLA2 inhibitors co
283 Ca(2+) was necessary but not sufficient for cPla2 translocation, and nuclear swelling was required i
285 mediating the p25-induced LPC production and cPLA2 upregulation is critical in triggering the p25-med
288 Furthermore, activation of both ERK1/2 and cPLA2 was dependent on chlamydial growth and restricted
292 ype and phosphorylation site mutant forms of cPLA2, we show that phosphorylation of cPLA2 at both Ser
293 osphorylation of Ser505 and Ser727 activates cPLA2, we systematically analyzed the effects of S505A,
294 tern analyses revealed that these changes in cPLA2 were accompanied by a time-dependent gel shift of
297 through at least two pathways, TNF-alpha and cPLA2, which are both also critical for antimycobacteria
299 the C2 domain in cytosolic phospholipase A2 (cPLA2) with the CARD domain in mitochondrial antiviral s
300 r) inhibited the phosphorylation of ERKs and cPLA2 without inhibition of several other tyrosine phosp