Lipocortin inhibition of extracellular and intracellular phospholipases A<sub>2</sub> is substrate concentration dependent

Aarsman, A.J.; Mynbeek, G.; Bosch, H. van den; Rothhut, Bernard; Prieur, Benoît E.; Coméra, Christine; Jordan, Lynda; Russo‐Marie, Françoise

doi:10.1016/0014-5793(87)81212-7

Cited by 113 publications

(28 citation statements)

References 26 publications

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“…However, subsequent studies failed to demonstrate any direct interaction between the 14-kDa PLA 2 and annexins. Instead, it was found that the in vitro inhibition of 14-kDa PLA 2 by annexins could be overcome by increasing the substrate concentrations (41,(62)(63)(64). The extent of inhibition was more closely related to the inhibitor:substrate rather than the inhibitor:enzyme ratio, and the kinetics of inhibition were not compatible with a simple competitive or noncompetitive pattern.…”

Section: P11 Interacts With and Inhibits Cytosolic Phospholipase Amentioning

confidence: 99%

p11, a Unique Member of the S100 Family of Calcium-binding Proteins, Interacts with and Inhibits the Activity of the 85-kDa Cytosolic Phospholipase A2

Angus

Yao

et al. 1997

Journal of Biological Chemistry

108

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Using a two hybrid system screen of a human cDNA library, we have found that p11, a unique member of the S100 family of calcium-binding proteins, interacts with the carboxyl region of the 85-kDa cytosolic phospholipase A 2 (cPLA 2 ). p11 synthesized in a cell-free system interacts with cPLA 2 in vitro. The p11-cPLA 2 complex is detectable from a human bronchial epithelial cell line (BEAS 2B). Furthermore, p11 inhibits cPLA 2 activity in vitro. Selective inhibition of p11 expression in the BEAS 2B cells by antisense RNA results in an increased PLA 2 activity as well as an increased release of prelabeled arachidonic acid. This study demonstrates a novel mechanism for the regulation of cPLA 2 by an S100 protein.

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Section: P11 Interacts With and Inhibits Cytosolic Phospholipase Amentioning

confidence: 99%

p11, a Unique Member of the S100 Family of Calcium-binding Proteins, Interacts with and Inhibits the Activity of the 85-kDa Cytosolic Phospholipase A2

Angus

Yao

et al. 1997

Journal of Biological Chemistry

108

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“…(12,18). (ii) The intracellular class of PLA 2 is composed of a Ca 2ϩ -independent PLA 2 (iPLA 2 ) involved essentially in regulating the incorporation of AA into membrane phospholipids (19,20), and of the group IV cytosolic 85-kDa Ca 2ϩ -dependent PLA 2 (cPLA 2 ) responsible of intracellular AA release (16,20,21).…”

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confidence: 99%

Inhibition of Cytosolic Phospholipase A2 by Annexin V in Differentiated Permeabilized HL-60 Cells

Mira

Dubois

Oudinet

et al. 1997

Journal of Biological Chemistry

107

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Annexin V belongs to a family of proteins that interact with phospholipids in a Ca 2؉ -dependent manner. This protein has been demonstrated to have anti-phospholipase A 2 activity. However, this effect has never yet been reported with the 85-kDa cytosolic PLA 2 (cPLA 2 ). We studied, in a model of differentiated and streptolysin O-permeabilized HL-60 cells, the effect of annexin V on cPLA 2 activity after stimulation by calcium, GTP␥S (guanosine 5-O-(3-thiotriphosphate)), formyl-Met-LeuPhe, or phorbol 12-myristate 13-acetate. Both recombinant and human placental purified annexin V inhibit cPLA 2 activity whatever the stimulus used. The decrease of arachidonic acid release is of 40 and 50%, respectively, at [Ca 2؉ ] of 3 and 10 M. The mechanism of inhibition was also analyzed. cPLA 2 requires calcium and protein kinase C (PKC) or mitogen-activated protein kinase phosphorylation for its activation. As annexin V was shown to be an endogenous inhibitor of PKC, PKC-stimulated cPLA 2 activity was analyzed. Using GF109203x, a specific PKC inhibitor, we demonstrated that this pathway is of minor importance in our model. cPLA 2 inhibition by annexin V is not linked to PKC inhibition. To test the hypothesis of phospholipid depletion, mutants of annexin V were constructed using mutagenesis directed to Ca 2؉ site. We demonstrate that the Ca 2؉ site located in domain I is necessary for the inhibitory effect of annexin V on cPLA 2 activity. The site in domain IV is also involved but with less efficiency. In contrast, mutations in site II and III do not modify this effect. Moreover, annexin V mutated on all sites does not inhibit cPLA 2 . Thus, we propose a predominant role of module (I/IV) in the biological action of annexin V, which, in physiological conditions, may control cPLA 2 activity by depletion of the phospholipid substrate.

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“…Although PKC and annexins have some features in common, such as binding of Ca2+ and phospholipids and onto cytoskeletal elements, there are no structural similarities between them. Numerous roles have been attributed to annexins, including anti-phospholipase A, (Davidson et al, 1987 ;Aarsman et al, 1987), anti-coagulant (Funakoshi et al, 1987;Maurer-Fogy et al, 1988) and anti-inflammatory activities (Miele et al, 1988;Errasfa et al, 1989;Cirino et al, 1989). All these functions occur extracellularly but annexins are mainly intracellular proteins so that their exact function within the cell still remains a matter of debate.…”

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Inhibitory Effect of Annexin V on Protein Kinase C Activity in Mesangial Cell Lysates

Rothhut

Dubois

Féliers

et al. 1995

European Journal of Biochemistry

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U 96 INSERM, Le Kremlin-Bicetre, FranceAnnexin V belongs to a large family of calcium-binding and phospholipid-binding proteins and may act as an endogenous regulator of the protein kinase C (PKC) activity. This study examines the effect of annexin V on the in v i m PKC activity in cultured mesangial cells using histone H1, the peptide [Ser25]PKC-(19-31), or endogenous proteins as substrates. The SDS/PAGE pattern of "P-labeled mesangial proteins showed that the calcium-independent PKC [(n+a)PKC] phosphorylated several proteins from 70 kDa to 40 kDa and 22 kDa to 15 kDa. Three additional proteins from 34 kDa to 29 kDa, including annexin I and its proteolytic forms, were detected after activation of calcium-dependent PKC (cPKC). Increasing concentrations of annexin V did not alter the phosphorylation of (n+a)PKC substrates. By contrast, specific phosphorylation of proteins and annexin I by cPKC, was reduced in a dose-dependent manner. Addition of high concentration of calcium and phosphatidylserine did not reverse the inhibitory effect of annexin V. Annexin V also inhibited the phosphorylation of histone HI or peptide [Ser25]PKC-(19-31) by cPKC. Moreover, removal of annexin V from cytosols increased the annexin I phosphorylation by these isoforms. From these results, we propose that annexin V may regulate the signal-transduction pathway involving the activation of cPKC, as they act in vitro as an inhibitor of these kinases.

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Lipocortin inhibition of extracellular and intracellular phospholipases A₂ is substrate concentration dependent

Cited by 113 publications

References 26 publications

p11, a Unique Member of the S100 Family of Calcium-binding Proteins, Interacts with and Inhibits the Activity of the 85-kDa Cytosolic Phospholipase A2

p11, a Unique Member of the S100 Family of Calcium-binding Proteins, Interacts with and Inhibits the Activity of the 85-kDa Cytosolic Phospholipase A2

Inhibition of Cytosolic Phospholipase A2 by Annexin V in Differentiated Permeabilized HL-60 Cells

Inhibitory Effect of Annexin V on Protein Kinase C Activity in Mesangial Cell Lysates

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Lipocortin inhibition of extracellular and intracellular phospholipases A2 is substrate concentration dependent

Cited by 113 publications

References 26 publications

p11, a Unique Member of the S100 Family of Calcium-binding Proteins, Interacts with and Inhibits the Activity of the 85-kDa Cytosolic Phospholipase A2

p11, a Unique Member of the S100 Family of Calcium-binding Proteins, Interacts with and Inhibits the Activity of the 85-kDa Cytosolic Phospholipase A2

Inhibition of Cytosolic Phospholipase A2 by Annexin V in Differentiated Permeabilized HL-60 Cells

Inhibitory Effect of Annexin V on Protein Kinase C Activity in Mesangial Cell Lysates

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Lipocortin inhibition of extracellular and intracellular phospholipases A₂ is substrate concentration dependent