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Phosphorylation of cPLA(2)α at Ser(505) Is Necessary for Its Translocation to PtdInsP(2)-Enriched Membranes

Group IVA cytosolic phospholipase A(2)α (cPLA(2)α) is a key enzyme in physiology and pathophysiology because it constitutes a rate-limiting step in the pathway for the generation of pro- and anti-inflammatory eicosanoid lipid mediators. cPLA(2)α activity is tightly regulated by multiple factors, inc...

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Autores principales: Casas, Javier, Balsinde, Jesús, Balboa, María A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000823/
https://www.ncbi.nlm.nih.gov/pubmed/35408744
http://dx.doi.org/10.3390/molecules27072347
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author Casas, Javier
Balsinde, Jesús
Balboa, María A.
author_facet Casas, Javier
Balsinde, Jesús
Balboa, María A.
author_sort Casas, Javier
collection PubMed
description Group IVA cytosolic phospholipase A(2)α (cPLA(2)α) is a key enzyme in physiology and pathophysiology because it constitutes a rate-limiting step in the pathway for the generation of pro- and anti-inflammatory eicosanoid lipid mediators. cPLA(2)α activity is tightly regulated by multiple factors, including the intracellular Ca(2+) concentration, phosphorylation reactions, and cellular phosphatidylinositol (4,5) bisphosphate levels (PtdInsP(2)). In the present work, we demonstrate that phosphorylation of the enzyme at Ser(505) is an important step for the translocation of the enzyme to PtdInsP(2)–enriched membranes in human cells. Constructs of eGFP-cPLA(2) mutated in Ser(505) to Ala (S505A) exhibit a delayed translocation in response to elevated intracellular Ca(2+), and also in response to increases in intracellular PtdInsP(2) levels. Conversely, translocation of a phosphorylation mimic mutant (S505E) is fully observed in response to cellular increases in PtdInsP(2) levels. Collectively, these results suggest that phosphorylation of cPLA(2)α at Ser(505) is necessary for the enzyme to translocate to internal membranes and mobilize arachidonic acid for eicosanoid synthesis.
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spelling pubmed-90008232022-04-12 Phosphorylation of cPLA(2)α at Ser(505) Is Necessary for Its Translocation to PtdInsP(2)-Enriched Membranes Casas, Javier Balsinde, Jesús Balboa, María A. Molecules Article Group IVA cytosolic phospholipase A(2)α (cPLA(2)α) is a key enzyme in physiology and pathophysiology because it constitutes a rate-limiting step in the pathway for the generation of pro- and anti-inflammatory eicosanoid lipid mediators. cPLA(2)α activity is tightly regulated by multiple factors, including the intracellular Ca(2+) concentration, phosphorylation reactions, and cellular phosphatidylinositol (4,5) bisphosphate levels (PtdInsP(2)). In the present work, we demonstrate that phosphorylation of the enzyme at Ser(505) is an important step for the translocation of the enzyme to PtdInsP(2)–enriched membranes in human cells. Constructs of eGFP-cPLA(2) mutated in Ser(505) to Ala (S505A) exhibit a delayed translocation in response to elevated intracellular Ca(2+), and also in response to increases in intracellular PtdInsP(2) levels. Conversely, translocation of a phosphorylation mimic mutant (S505E) is fully observed in response to cellular increases in PtdInsP(2) levels. Collectively, these results suggest that phosphorylation of cPLA(2)α at Ser(505) is necessary for the enzyme to translocate to internal membranes and mobilize arachidonic acid for eicosanoid synthesis. MDPI 2022-04-06 /pmc/articles/PMC9000823/ /pubmed/35408744 http://dx.doi.org/10.3390/molecules27072347 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Casas, Javier
Balsinde, Jesús
Balboa, María A.
Phosphorylation of cPLA(2)α at Ser(505) Is Necessary for Its Translocation to PtdInsP(2)-Enriched Membranes
title Phosphorylation of cPLA(2)α at Ser(505) Is Necessary for Its Translocation to PtdInsP(2)-Enriched Membranes
title_full Phosphorylation of cPLA(2)α at Ser(505) Is Necessary for Its Translocation to PtdInsP(2)-Enriched Membranes
title_fullStr Phosphorylation of cPLA(2)α at Ser(505) Is Necessary for Its Translocation to PtdInsP(2)-Enriched Membranes
title_full_unstemmed Phosphorylation of cPLA(2)α at Ser(505) Is Necessary for Its Translocation to PtdInsP(2)-Enriched Membranes
title_short Phosphorylation of cPLA(2)α at Ser(505) Is Necessary for Its Translocation to PtdInsP(2)-Enriched Membranes
title_sort phosphorylation of cpla(2)α at ser(505) is necessary for its translocation to ptdinsp(2)-enriched membranes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000823/
https://www.ncbi.nlm.nih.gov/pubmed/35408744
http://dx.doi.org/10.3390/molecules27072347
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