Intracellular Calcium Signals Regulating Cytosolic Phospholipase A2 Translocation to Internal Membranes

Evans, John H.; Spencer, Diane M; Zweifach, Adam; Leslie, Christina C.

doi:10.1074/jbc.m100943200

Cited by 236 publications

(244 citation statements)

References 51 publications

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“…Subcellular Targeting of cPLA 2 -C2 and PKC-␣-C2-It has been known that conventional PKCs and their C2 domains, including PKC-␥ and its C2 domain (37), PKC-␣ (41), and PKC-␣-C2 (20), translocate to plasma membrane in response to [Ca 2ϩ ] i spikes, whereas cPLA 2 -C2 and cPLA 2 are targeted to the perinuclear region upon Ca 2ϩ import (21,22,43). However, the origin of these differential subcellular targeting behaviors of PKC C2 domains, cPLA 2 -C2, and their host proteins is relatively poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Also, this subcellular localization pattern of isolated C2 domains correlates with that of peripheral proteins harboring the C2 domains; i.e. conventional PKCs translocate to plasma membrane (38 -41) while cPLA 2 moves to perinuclear region (42,43). Although vesicles used in the preceding measurements serve well for determining the lipid selectivity of the C2 domains and mutants, they do not fully represent the cytoplasmic plasma membrane and the cytoplasmic nuclear envelope that PKC-␣-C2 and for cPLA 2 -C2, respectively, are targeted to.…”

Section: Ps Selectivity Of Pkc-␣-c2-mentioning

confidence: 99%

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The Molecular Basis of Differential Subcellular Localization of C2 Domains of Protein Kinase C-α and Group IVa Cytosolic Phospholipase A2

Stahelin

Rafter

Das

et al. 2003

Journal of Biological Chemistry

119

192

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The C2 domain is a Ca 2؉ -dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. C2 domains are unique among membrane targeting domains in that they show a wide range of lipid selectivity for the major components of cell membranes, including phosphatidylserine and phosphatidylcholine. To understand how C2 domains show diverse lipid selectivity and how this functional diversity affects their subcellular targeting behaviors, we measured the binding of the C2 domains of group IVa cytosolic phospholipase A 2 (cPLA 2 ) and protein kinase C-␣ (PKC-␣) to vesicles that model cell membranes they are targeted to, and we monitored their subcellular targeting in living cells. The surface plasmon resonance analysis indicates that the PKC-␣ C2 domain strongly prefers the cytoplasmic plasma membrane mimic to the nuclear membrane mimic due to high phosphatidylserine content in the former and that Asn 189 plays a key role in this specificity. In contrast, the cPLA 2 C2 domain has specificity for the nuclear membrane mimic over the cytoplasmic plasma membrane mimic due to high phosphatidylcholine content in the former and aromatic and hydrophobic residues in the calcium binding loops of the cPLA 2 C2 domain are important for its lipid specificity. The subcellular localization of enhanced green fluorescent protein-tagged C2 domains and mutants transfected into HEK293 cells showed that the subcellular localization of the C2 domains is consistent with their lipid specificity and could be tailored by altering their in vitro lipid specificity. The relative cell membrane translocation rate of selected C2 domains was also consistent with their relative affinity for model membranes. Together, these results suggest that biophysical principles that govern the in vitro membrane binding of C2 domains can account for most of their subcellular targeting properties.The agonist-induced subcellular targeting of protein is an important process in cell signaling and regulation. Recently, the membrane targeting of peripheral proteins (e.g. phospholipases, lipid-dependent protein kinases, lipid kinases, and lipid phosphatases) by Ca 2ϩ and lipid mediators, including phosphoinositides, has received much attention as an important event in cell signaling and membrane trafficking. It has been shown that the subcellular targeting of peripheral proteins is driven by a growing number of membrane targeting domains. These domains include protein kinase C (PKC) 1 conserved 1 (C1) domain, PKC conserved 2 (C2) domain, pleckstrin homology (PH) domain, Fab1, YOTB, Vac 1 and EEA1 (FYVE) domain, band four-point-one, ezrin, radixin and moesin (FERM) domain, epsin amino-terminal homology (ENTH) domain, and phox (PX) domains (1-5).The C2 domain has been identified in many cellular proteins involved in signal transduction or membrane trafficking (5-7). A majority of C2 domains bind the membrane in a Ca 2ϩ -dependent manner and thereby play an important role in Ca 2ϩ -dependent membrane targeting of pe...

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Section: Discussionmentioning

confidence: 99%

Section: Ps Selectivity Of Pkc-␣-c2-mentioning

confidence: 99%

The Molecular Basis of Differential Subcellular Localization of C2 Domains of Protein Kinase C-α and Group IVa Cytosolic Phospholipase A2

Stahelin

Rafter

Das

et al. 2003

Journal of Biological Chemistry

119

192

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“…Calcium promotes cytosol-to-membrane relocation of the cPLA 2 -α protein by binding to the C2-domain [13][14][15]. However, cPLA 2 -α targeting to membranes by calcium ions is complex since it is dependent both on the amplitude and the duration of the calcium increase [16,17]. The catalytic domain can affect membrane association of the enzyme by modulating the rate of association and also the residence time at membranes [18].…”

Section: Introductionmentioning

confidence: 99%

Polychlorinated biphenyls induce arachidonic acid release in human platelets in a tamoxifen sensitive manner via activation of group IVA cytosolic phospholipase A2-α

Forsell

Olsson

Andersson

et al. 2005

Biochemical Pharmacology

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Polychlorinated biphenyls (PCBs) are stable compounds commonly found in nature as environmental pollutants. PCBs can affect the endocrine function of hormones such as steroid-hormones. Also, PCBs are known to be inducers of arachidonic acid release in various cells. We report, here, the effects of PCBs on eicosanoid formation, arachidonic acid release and cytosolic phospholipase A 2 -α(cPLA 2 -α) activation in human platelets. Ortho-substituted PCBs induced a time and dosedependent release of arachidonic acid and the concomitant formation of 12(S)-hydroxy-5,8-cis-10-trans-14-cis-eicosatetraenoic acid (12-HETE) and 12(S)-hydroxy-5-cis-8,10-transheptadecatrienoic acid (12-HHT) in human platelets. The release of arachidonic acid and the formation of 12-HETE was completely blocked by the cPLA 2 -α inhibitors AACOCF 3 or pyrrolidine-1. PCB-treatment of platelets demonstrated that the cPLA 2 -α protein as well as PLA 2 activity translocated to the membrane fraction, independent of a rise in intracellular Ca 2+ . Furthermore, electrophoretic gel mobility shift analysis of cPLA 2 -α on SDS-PAGE demonstrated a PCB-dependent phosphorylation of cPLA 2 -α. The effects of 17β-estradiol and two structurally unrelated anti-estrogens, nafoxidin and tamoxifen on PCB-induced arachidonic acid release in platelets were also investigated. Both nafoxidin and tamoxifen inhibited PCB-induced arachidonic acid release as well as 12-HETE and 12-HHT formation. Interestingly, platelets incubated with PCBs did not aggregate despite the fact that robust release of arachidonic acid was observed. In summary, these results demonstrate that certain PCBs induce activation of cPLA 2 -α independent of a rise in intracellular calcium and a robust release of arachidonic acid release with resulting eicosanoid formation in human platelets.

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“…8B) (59). An increase in [Ca 2ϩ ] i is a critical step for cPLA 2 ␣ to translocate from the cytosol to perinuclear membranes for initiation of stimuluscoupled AA release (60,61). Fig.…”

Section: Role Of Constitutively Activated Erk1/2 On H 2 O 2 -Induced Aamentioning

confidence: 99%

Cross-talk between Cytosolic Phospholipase A2α (cPLA2α) and Secretory Phospholipase A2 (sPLA2) in Hydrogen Peroxide-induced Arachidonic Acid Release in Murine Mesangial Cells

Han¹,

Sapirstein

Hung³

et al. 2003

Journal of Biological Chemistry

144

111

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Intracellular Calcium Signals Regulating Cytosolic Phospholipase A2 Translocation to Internal Membranes

Abstract: Increased intracellular

Cited by 236 publications

References 51 publications

The Molecular Basis of Differential Subcellular Localization of C2 Domains of Protein Kinase C-α and Group IVa Cytosolic Phospholipase A2

The Molecular Basis of Differential Subcellular Localization of C2 Domains of Protein Kinase C-α and Group IVa Cytosolic Phospholipase A2

Polychlorinated biphenyls induce arachidonic acid release in human platelets in a tamoxifen sensitive manner via activation of group IVA cytosolic phospholipase A2-α

Cross-talk between Cytosolic Phospholipase A2α (cPLA2α) and Secretory Phospholipase A2 (sPLA2) in Hydrogen Peroxide-induced Arachidonic Acid Release in Murine Mesangial Cells

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