Phosphatidylinositol 3-kinase activity negatively regulates stability of cyclooxygenase 2 mRNA

Martha M Monick; Pamela K Robeff; Noah S Butler; Dawn M Flaherty; A Brent Carter; Michael W Peterson; Gary W Hunninghake

doi:10.1074/jbc.M203218200

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Phosphatidylinositol 3-kinase activity negatively regulates stability of cyclooxygenase 2 mRNA

Journal article

Open access

Peer reviewed

Phosphatidylinositol 3-kinase activity negatively regulates stability of cyclooxygenase 2 mRNA

Martha M Monick, Pamela K Robeff, Noah S Butler, Dawn M Flaherty, A Brent Carter, Michael W Peterson and Gary W Hunninghake

The Journal of biological chemistry, Vol.277(36), pp.32992-33000

09/06/2002

DOI: 10.1074/jbc.M203218200

PMID: 12072439

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Abstract

Human alveolar macrophages have both lipopolysaccharide (LPS)-induced and constitutive phosphatidylinositol 3-kinase (PI3K) activity. We observed that blocking PI3K activity increased release of prostaglandin E2 after LPS exposure, and increasing PI3K activity (interleukin-13) decreased release of prostaglandin E2 after LPS exposure. This was not because of an effect of PI3K on phospholipase 2 activity. PI3K inhibition resulted in an increase in cyclooxygenase 2 (COX2) protein, mRNA, and mRNA stability. PI3K negatively regulated activation of the p38 pathway (p38, MKK3/6, and MAPKAP2), and an active p38 was necessary for COX2 production. The data suggest that PI3K inhibition of p38 modulates COX2 expression via destabilization of LPS-induced COX2 mRNA.

Protein-Tyrosine Kinases - metabolism

Cyclooxygenase 2

Humans

Phosphatidylinositol 3-Kinases - metabolism

MAP Kinase Kinase 3

RNA, Messenger - metabolism

Mitogen-Activated Protein Kinase Kinases - metabolism

Time Factors

Isoenzymes - metabolism

p38 Mitogen-Activated Protein Kinases

Prostaglandin-Endoperoxide Synthases - genetics

Isoenzymes - genetics

Cells, Cultured

Enzyme Inhibitors - pharmacology

Interleukin-13 - pharmacology

RNA Stability

Reverse Transcriptase Polymerase Chain Reaction

Dinoprostone - metabolism

Gene Expression Regulation, Enzymologic

Membrane Proteins

Animals

Models, Biological

Prostaglandin-Endoperoxide Synthases - metabolism

Lipopolysaccharides - pharmacology

Mice

Enzyme Activation

Dactinomycin - pharmacology

Mitogen-Activated Protein Kinases - metabolism

Details

Title: Subtitle: Phosphatidylinositol 3-kinase activity negatively regulates stability of cyclooxygenase 2 mRNA
Creators: Martha M Monick - University of Iowa Roy J. and Lucille A. Carver College of Medicine and Veterans Administration Medical Center, Iowa City, Iowa 52242, USA. matha.monick@uiowa.edu
Pamela K Robeff
Noah S Butler
Dawn M Flaherty
A Brent Carter
Michael W Peterson
Gary W Hunninghake
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(36), pp.32992-33000
DOI: 10.1074/jbc.M203218200
PMID: 12072439
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: HL-60316 / NHLBI NIH HHS ES-09607 / NIEHS NIH HHS HL-03860 / NHLBI NIH HHS RR00059 / NCRR NIH HHS
Language: English
Date published: 09/06/2002
Academic Unit: Microbiology and Immunology; Radiation Oncology; Internal Medicine
Record Identifier: 9984001162002771

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