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PMID: 1631101 Published · ppublish English Journal Article

Cytosolic phospholipase A2 is coupled to hormonally regulated release of arachidonic acid.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 13 ·1992-07-01 ·Pages 6147-51

Lin LL, Lin AY, Knopf JL

Abstract

Cytosolic phospholipase A2 (cPLA2) binds to natural membrane vesicles in a Ca(2+)-dependent fashion, resulting in the selective release of arachidonic acid, thus implicating cPLA2 in the hormonally regulated production of eicosanoids. Here we report that the treatment of Chinese hamster ovary (CHO) cells overexpressing cPLA2 with ATP or thrombin resulted in an increased release of arachidonic acid as compared with parental CHO cells, demonstrating the hormonal coupling of cPLA2. In contrast, CHO cells overexpressing a secreted form of mammalian PLA2 (sPLA2-II) failed to show any increased hormonal responsiveness. Interestingly, we have noted that the activation of cPLA2 with a wide variety of agents stimulates the phosphorylation of cPLA2 on serine residues. Pretreatment of cells with staurosporin blocked the ATP-mediated phosphorylation of cPLA2 and strongly inhibited the activation of the enzyme. Increased cPLA2 activity was also observed in lysates prepared from ATP-treated cells and was sensitive to phosphatase treatment. These results suggest that in addition to Ca2+, the phosphorylation of cPLA2 plays an important role in the agonist-induced activation of cPLA2.

MeSH Terms
Adenosine Triphosphate/pharmacology Alkaloids/pharmacology Animals Arachidonic Acid/metabolism CHO Cells Calcimycin/pharmacology Calcium/physiology Cricetinae Cytosol/enzymology Enzyme Activation/drug effects Epidermal Growth Factor/pharmacology In Vitro Techniques Phospholipases A/metabolism Phospholipases A2 Phosphoproteins/metabolism Phosphorylation Platelet-Derived Growth Factor/pharmacology Staurosporine Tetradecanoylphorbol Acetate/pharmacology Thrombin/pharmacology
Chemicals
Alkaloids Phosphoproteins Platelet-Derived Growth Factor Arachidonic Acid Calcimycin Epidermal Growth Factor Adenosine Triphosphate Phospholipases A Phospholipases A2 Thrombin Staurosporine Tetradecanoylphorbol Acetate Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lin L L
Genetics Institute, Inc., Cambridge, MA 02140.
Lin A Y
Knopf J L
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26 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.13.6147
Published
1992-07-01
Pages
6147-51
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC402139
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.89.13.6147 PMC Full Text View journal details
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