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

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services 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 Zamorano, J. Articles by Keegan, A. D. Search for Related Content PubMed PubMed Citation Articles by Zamorano, J. Articles by Keegan, A. D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LECITHIN VANADIUM COMPOUNDS

Phosphatidylcholine-Specific Phospholipase C Activity Is Necessary for the Activation of STAT6 ¹

Jose Zamorano^2,*, Maria Dolores Rivas^*, Antonio Garcia-Trinidad^*, Cheng-Kui Qu and Achsah D. Keegan

^* Unidad de Investigacion, Hospital San Pedro de Alcantara, Caceres, Spain; and Departments of Hematopoiesis and Immunology, Holland Laboratory, American Red Cross, Rockville, MD 20855

It is well established that Janus kinase (JAK) tyrosine kinases play a key role in the activation of STAT6 by IL-4. In this study, we investigated additional molecules involved in this process. We previously found that IL-4 and TNF- cooperate in the activation of STAT6 and NF-B, suggesting that these transcription factors are regulated by common intracellular signaling pathways. To test this hypothesis, we analyzed the effect of known inhibitors of NF-B on the activation of STAT6. We discovered that inhibitors of phosphatidylcholine-specific phospholipase C (PC-PLC), but not other lipases, blocked the activation of STAT6 by IL-4. The activation of PC-PLC seems to be an early event in IL-4 signaling, because its inhibition abrogated JAK activation and STAT6 tyrosine phosphorylation. Interestingly, we found that the effects of pervanadate and sodium orthovanadate on STAT6 activation correspond to their effect on PC-PLC. Thus, pervanadate by itself activated PC-PLC, JAK, and STAT6, whereas sodium orthovanadate suppressed PC-PLC, JAK, and STAT6 activation by IL-4. We further found that PC-PLC activation is necessary but not sufficient to promote STAT6 activation, and therefore, additional intracellular pathways regulated by IL-4 and pervanadate may collaborate with PC-PLC to signal STAT6 activation. It has been reported that IL-4 signals PC-PLC activation; in this study, we provide evidence that this phospholipase plays a key role in IL-4 signaling.

This article has been cited by other articles:

				H. Liu, H. Zhang, and H. J. Forman Silica Induces Macrophage Cytokines through Phosphatidylcholine-Specific Phospholipase C with Hydrogen Peroxide Am. J. Respir. Cell Mol. Biol., May 1, 2007; 36(5): 594 - 599. [Abstract] [Full Text] [PDF]

				Y. Kato, C. A. Lambert, A. C. Colige, P. Mineur, A. Noel, F. Frankenne, J.-M. Foidart, M. Baba, R.-I. Hata, K. Miyazaki, et al. Acidic Extracellular pH Induces Matrix Metalloproteinase-9 Expression in Mouse Metastatic Melanoma Cells through the Phospholipase D-Mitogen-activated Protein Kinase Signaling J. Biol. Chem., March 25, 2005; 280(12): 10938 - 10944. [Abstract] [Full Text] [PDF]

				W. Chen, M. O. Daines, and G. K. K. Hershey Methylation of STAT6 Modulates STAT6 Phosphorylation, Nuclear Translocation, and DNA-Binding Activity J. Immunol., June 1, 2004; 172(11): 6744 - 6750. [Abstract] [Full Text] [PDF]