Sphingosine kinase mediates activation of extracellular signal-related kinase and Akt by respiratory syncytial virus

Martha M Monick; Kelli Cameron; Linda S Powers; Noah S Butler; Diann McCoy; Rama K Mallampalli; Gary W Hunninghake

doi:10.1165/rcmb.2003-0424OC

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Sphingosine kinase mediates activation of extracellular signal-related kinase and Akt by respiratory syncytial virus

Journal article

Peer reviewed

Sphingosine kinase mediates activation of extracellular signal-related kinase and Akt by respiratory syncytial virus

Martha M Monick, Kelli Cameron, Linda S Powers, Noah S Butler, Diann McCoy, Rama K Mallampalli and Gary W Hunninghake

American journal of respiratory cell and molecular biology, Vol.30(6), pp.844-852

06/2004

DOI: 10.1165/rcmb.2003-0424OC

PMID: 14742298

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Abstract

Respiratory syncytial virus (RSV) preferentially infects lung epithelial cells. Infected cells remain viable well into the infection. This prolonged survival results from RSV-induced activation of pro-survival pathways, including Akt and extracellular signal-related kinase (ERK). Sphingosine 1-phosphate (S1P) is a sphingolipid metabolite with demonstrated links to cell survival. It is enzymatically generated by sequential activation of ceramidase (generation of sphingosine) and sphingosine kinase (generation of S1P). In these studies, we found that RSV stimulated neutral ceramidase and sphingosine kinase activities in lung epithelial cells. The combined effect of activation of these two enzymes would decrease proapoptotic ceramide and increase antiapoptotic S1P. S1P activated Akt and ERK within minutes, and inhibition of sphingosine kinase blocked RSV-induced ERK and Akt activation, leading to accelerated cell death after viral infection. RSV infection does eventually kill infected cells but activation of cell survival pathways significantly delays cell death. The studies are the first evidence linking sphingolipid metabolites to cell survival mechanisms in the context of a viral infection.

Amidohydrolases - metabolism

Proto-Oncogene Proteins - metabolism

Cell Line

Lysophospholipids - metabolism

Epithelial Cells - metabolism

Respiratory Mucosa - cytology

Neutral Ceramidase

Humans

Protein-Serine-Threonine Kinases

Respiratory Syncytial Virus Infections

Phosphotransferases (Alcohol Group Acceptor) - metabolism

Proto-Oncogene Proteins c-akt

Sphingosine - analogs & derivatives

Animals

Ceramidases

Epithelial Cells - virology

Signal Transduction - physiology

Sphingosine - metabolism

Enzyme Activation

Epithelial Cells - cytology

Cell Survival - physiology

Respiratory Syncytial Viruses - metabolism

Mitogen-Activated Protein Kinases - metabolism

Details

Title: Subtitle: Sphingosine kinase mediates activation of extracellular signal-related kinase and Akt by respiratory syncytial virus
Creators: Martha M Monick - Division of Pulmonary, Critical Care, and Occupational Medicine, Room 100, EMRB, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. martha-monick@uiowa.edu
Kelli Cameron
Linda S Powers
Noah S Butler
Diann McCoy
Rama K Mallampalli
Gary W Hunninghake
Resource Type: Journal article
Publication Details: American journal of respiratory cell and molecular biology, Vol.30(6), pp.844-852
Publisher: United States
DOI: 10.1165/rcmb.2003-0424OC
PMID: 14742298
ISSN: 1044-1549
eISSN: 1535-4989
Grant note: HL 68135 / NHLBI NIH HHS HL-60316 / NHLBI NIH HHS ES-09607 / NIEHS NIH HHS HL-55584 / NHLBI NIH HHS RR00059 / NCRR NIH HHS
Language: English
Date published: 06/2004
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984001220202771

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