A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP
Abstract
We report the cloning and expression of a cDNA encoding a high molecular weight (85.2 kd) cytosolic phospholipase A2 (cPLA2) that has no detectable sequence homology with the secreted forms of PLA2. We show that cPLA2 selectively cleaves arachidonic acid from natural membrane vesicles and demonstrate that cPLA2 translocates to membrane vesicles in response to physiologically relevant changes in free calcium. Moreover, we demonstrate that an amino-terminal 140 amino acid fragment of cPLA2 translocates to natural membrane vesicles in a Ca(2+)-dependent fashion. Interestingly, we note that this 140 amino acid domain of cPLA2 contains a 45 amino acid region with homology to PKC, p65, GAP, and PLC. We suggest that this homology delineates a Ca(2+)-dependent phospholipid-binding motif, providing a mechanism for the second messenger Ca2+ to translocate and activate cytosolic proteins.
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Variation in nanomolar concentrations of intracellular Ca2+ impairs cPLA2 translocation to the cellular membrane and its subsequent activation.
“Since variation in nanomolar concentrations of intracellular Ca2+ impairs cPLA2 translocation to the cellular membrane and its subsequent activation (37)”
From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [37]
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- Authors
- Clark, J. D., Lin, L.-L., Kriz, R. W., Ramesha, C. S., Sultzman, L. A., Lin, A. Y., Milona, N., & Knopf, J. L.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1991-06
- Volume
- 65
- Issue
- 6
- Pages
- 1043-1051
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2051958752
- Cited by
- 1,688
- References
- 0
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 12 · 2023: 16 · 2022: 14 · 2021: 5 · 2020: 15 · 2019: 14 · 2018: 12 · 2017: 24 · 2016: 23 · 2015: 22 · 2014: 25 · 2013: 20 · 2012: 29
- FWCI
- 43.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- cytosolic phospholipase A2, arachidonic acid, translocation domain, membrane vesicles, protein activation, cDNA cloning
- MeSH terms
- Amino Acid Sequence, Arachidonic Acids, Base Sequence, Binding Sites, Calcium, Cell Compartmentation, Cell Membrane, Cloning, Molecular, Cytosol, Humans, Membrane Lipids, Molecular Sequence Data, Type C Phospholipases, Phospholipases A, Phospholipids, Protein Kinase C, Proteins, Substrate Specificity, Arachidonic Acid, GTPase-Activating Proteins, Phospholipases A2
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