HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 10, 9409-9416, March 5, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/10/9409    most recent M312008200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Su, H. Articles by Zhong, G. Search for Related Content PubMed PubMed Citation Articles by Su, H. Articles by Zhong, G. Social Bookmarking                      What's this?

Activation of Raf/MEK/ERK/cPLA2 Signaling Pathway Is Essential for Chlamydial Acquisition of Host Glycerophospholipids^*

Heng Su, Grant McClarty, Feng Dong, Grant M. Hatch¶, Zhixing K. Pan||, and Guangming Zhong**

From the Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, Departments of Medical Microbiology and ^¶Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba R3E OW3, Canada, and ^||Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio 43614

Chlamydiae, a diverse group of obligate intracellular pathogens replicating within cytoplasmic vacuoles of eukaryotic cells, are able to acquire lipids from host cells. Here we report that activation of the host Raf-MEK-ERK-cPLA2 signaling cascade is required for the chlamydial uptake of host glycerophospholipids. Both the MAP kinase pathway (Ras/Raf/MEK/ERK) and Ca²⁺-dependent cytosolic phospholipase A2 (cPLA2) were activated in chlamydia-infected cells. The inhibition of cPLA2 activity resulted in the blockade of the chlamydial uptake of host glycerophospholipids and impairment in chlamydial growth. Blocking either c-Raf-1 or MEK1/2 activity prevented the chlamydial activation of ERK1/2, leading to the suppression of both chlamydial activation of the host cPLA2 and uptake of glycerophospholipids from the host cells. The chlamydia-induced phosphorylation of cPLA2 was also blocked by a dominant negative ERK2. Furthermore, activation of both ERK1/2 and cPLA2 was dependent on chlamydial growth and restricted within chlamydia-infected cells, suggesting an active manipulation of the host ERK-cPLA2 signaling pathway by chlamydiae.

Received for publication, November 3, 2003 , and in revised form, December 3, 2003.

^* This work was supported in part by United States Department of Health Grants R01AI47997 and R01HL64883 (to G. Z.) and Canadian Institutes for Health Research Grant Gr-13301 (to G. M.). G. Z.'s and G. M.'s laboratories contributed equally to this work. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence should be addressed: Dept. of Microbiology and Immunology, University of Texas Health Science Ctr. at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229. Tel.: 210-567-1169; Fax: 210-567-0293; E-mail: Zhongg{at}UTHSCSA.EDU.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. G. Chu, S. K. Weeks, D. M. Gilligan, and D. D. Rockey Host {alpha}-adducin is redistributed and localized to the inclusion membrane in Chlamydia- and Chlamydophila-infected cells Microbiology, December 1, 2008; 154(12): 3848 - 3855. [Abstract] [Full Text] [PDF]

				C. B. Stone, D. L. Johnson, D. C. Bulir, J. D. Gilchrist, and J. B. Mahony Characterization of the Putative Type III Secretion ATPase CdsN (Cpn0707) of Chlamydophila pneumoniae J. Bacteriol., October 15, 2008; 190(20): 6580 - 6588. [Abstract] [Full Text] [PDF]

				Z. Li, D. Chen, Y. Zhong, S. Wang, and G. Zhong The Chlamydial Plasmid-Encoded Protein pgp3 Is Secreted into the Cytosol of Chlamydia-Infected Cells Infect. Immun., August 1, 2008; 76(8): 3415 - 3428. [Abstract] [Full Text] [PDF]

				K. L. Mumy, J. D. Bien, M. A. Pazos, K. Gronert, B. P. Hurley, and B. A. McCormick Distinct Isoforms of Phospholipase A2 Mediate the Ability of Salmonella enterica Serotype Typhimurium and Shigella flexneri To Induce the Transepithelial Migration of Neutrophils Infect. Immun., August 1, 2008; 76(8): 3614 - 3627. [Abstract] [Full Text] [PDF]

				J. L. Cocchiaro, Y. Kumar, E. R. Fischer, T. Hackstadt, and R. H. Valdivia From the Cover: Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole PNAS, July 8, 2008; 105(27): 9379 - 9384. [Abstract] [Full Text] [PDF]

				Z. Li, C. Chen, D. Chen, Y. Wu, Y. Zhong, and G. Zhong Characterization of Fifty Putative Inclusion Membrane Proteins Encoded in the Chlamydia trachomatis Genome Infect. Immun., June 1, 2008; 76(6): 2746 - 2757. [Abstract] [Full Text] [PDF]

				W. Cheng, P. Shivshankar, Y. Zhong, D. Chen, Z. Li, and G. Zhong Intracellular Interleukin-1{alpha} Mediates Interleukin-8 Production Induced by Chlamydia trachomatis Infection via a Mechanism Independent of Type I Interleukin-1 Receptor Infect. Immun., March 1, 2008; 76(3): 942 - 951. [Abstract] [Full Text] [PDF]

				P. Shivshankar, L. Lei, J. Wang, and G. Zhong Rottlerin Inhibits Chlamydial Intracellular Growth and Blocks Chlamydial Acquisition of Sphingolipids from Host Cells Appl. Envir. Microbiol., February 15, 2008; 74(4): 1243 - 1249. [Abstract] [Full Text] [PDF]

				K. R. Buchholz and R. S. Stephens The Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway Induces the Inflammatory Factor Interleukin-8 following Chlamydia trachomatis Infection Infect. Immun., December 1, 2007; 75(12): 5924 - 5929. [Abstract] [Full Text] [PDF]

				G. Wang, F. Burczynski, J. Anderson, and G. Zhong Effect of host fatty acid-binding protein and fatty acid uptake on growth of Chlamydia trachomatis L2 Microbiology, June 1, 2007; 153(6): 1935 - 1939. [Abstract] [Full Text] [PDF]

				R. Flores, J. Luo, D. Chen, G. Sturgeon, P. Shivshankar, Y. Zhong, and G. Zhong Characterization of the hypothetical protein Cpn1027, a newly identified inclusion membrane protein unique to Chlamydia pneumoniae Microbiology, March 1, 2007; 153(3): 777 - 786. [Abstract] [Full Text] [PDF]

				J. Luo, T. Jia, R. Flores, D. Chen, and G. Zhong Hypothetical Protein Cpn0308 Is Localized in the Chlamydia pneumoniae Inclusion Membrane Infect. Immun., January 1, 2007; 75(1): 497 - 503. [Abstract] [Full Text] [PDF]

				F. Dong, R. Flores, D. Chen, J. Luo, Y. Zhong, Z. Wu, and G. Zhong Localization of the Hypothetical Protein Cpn0797 in the Cytoplasm of Chlamydia pneumoniae-Infected Host Cells. Infect. Immun., November 1, 2006; 74(11): 6479 - 6486. [Abstract] [Full Text] [PDF]

				C. Chen, D. Chen, J. Sharma, W. Cheng, Y. Zhong, K. Liu, J. Jensen, R. Shain, B. Arulanandam, and G. Zhong The Hypothetical Protein CT813 Is Localized in the Chlamydia trachomatis Inclusion Membrane and Is Immunogenic in Women Urogenitally Infected with C. trachomatis. Infect. Immun., August 1, 2006; 74(8): 4826 - 4840. [Abstract] [Full Text] [PDF]

				J. Sharma, Y. Zhong, F. Dong, J. M. Piper, G. Wang, and G. Zhong Profiling of Human Antibody Responses to Chlamydia trachomatis Urogenital Tract Infection Using Microplates Arrayed with 156 Chlamydial Fusion Proteins Infect. Immun., March 1, 2006; 74(3): 1490 - 1499. [Abstract] [Full Text] [PDF]

				E. Y. Fukuda, S. P. Lad, D. P. Mikolon, M. Iacobelli-Martinez, and E. Li Activation of Lipid Metabolism Contributes to Interleukin-8 Production during Chlamydia trachomatis Infection of Cervical Epithelial Cells Infect. Immun., July 1, 2005; 73(7): 4017 - 4024. [Abstract] [Full Text] [PDF]

				S. P. Lad, E. Y. Fukuda, J. Li, L. M. de la Maza, and E. Li Up-Regulation of the JAK/STAT1 Signal Pathway during Chlamydia trachomatis Infection J. Immunol., June 1, 2005; 174(11): 7186 - 7193. [Abstract] [Full Text] [PDF]

				Y. Xiao, Y. Zhong, H. Su, Z. Zhou, P. Chiao, and G. Zhong NF-{kappa}B Activation Is Not Required for Chlamydia trachomatis Inhibition of Host Epithelial Cell Apoptosis J. Immunol., February 1, 2005; 174(3): 1701 - 1708. [Abstract] [Full Text] [PDF]

				J. Sharma, A. M. Bosnic, J. M. Piper, and G. Zhong Human Antibody Responses to a Chlamydia-Secreted Protease Factor Infect. Immun., December 1, 2004; 72(12): 7164 - 7171. [Abstract] [Full Text] [PDF]