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

J. Biol. Chem., Vol. 276, Issue 29, 27246-27255, July 20, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/29/27246    most recent M103250200v1 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 Hii, C. S. T. Articles by Ferrante, A. Search for Related Content PubMed PubMed Citation Articles by Hii, C. S. T. Articles by Ferrante, A. Social Bookmarking                      What's this?

Activation of the Phosphatidylinositol 3-Kinase-Akt/Protein Kinase B Signaling Pathway in Arachidonic Acid-stimulated Human Myeloid and Endothelial Cells
INVOLVEMENT OF THE ErbB RECEPTOR FAMILY^*

Charles S. T. Hii^§, Nahid Moghadammi, Andrew Dunbar^¶, and Antonio Ferrante^**

From the  Department of Immunopathology, Women's and Children's Hospital, North Adelaide 5006, South Australia, the ^¶ Molecular and Cellular Biology Laboratory, Cooperative Research Center for Tissue Growth and Repair, Commonwealth Scientific and Industrial Research Organization, Division of Health Sciences and Nutrition, Thebarton 5031, South Australia, the  Department of Paediatrics, University of Adelaide, Adelaide 5005, South Australia, and the ^** School of Pharmaceutical, Molecular and Biomedical Sciences, University of South Australia, Adelaide 5001, South Australia

Although arachidonic acid has been demonstrated to stimulate a wide variety of cellular functions, the responsible mechanisms remain poorly defined. We now report that arachidonic acid stimulated the activity of class Ia phosphatidylinositol 3-kinase (PI3K) in human umbilical vein endothelial cells, HL60 cells, and human neutrophils. Pretreatment of endothelial cells with AG-1478, an inhibitor of the ErbB receptor family, resulted in the suppression of PI3K activation by arachidonic acid. The fatty acid enhanced the tyrosine phosphorylation of ErbB4 but not of ErbB2 or ErbB3. The ability of arachidonic acid to stimulate PI3K activity in neutrophils was suppressed by indomethacin and nordihydroguaiaretic acid, inhibitors of the cyclooxygenases and lipoxygenases, respectively, but not by 17-octadecynoic acid, an inhibitor of -hydroxylation of arachidonic acid by cytochrome P450 monooxygenases. Consistent with this, the activity of PI3K in neutrophils was stimulated by 5-hydroxyeicosatetraenoic acid. Arachidonic acid also transiently stimulated the phosphorylation of Akt on Thr-308 and Ser-473. Although PI3K was not required for the activation of the mitogen-activated protein kinases, ERK1, ERK2, and p38, in arachidonic acid-stimulated neutrophils, the fatty acid acted via PI3K to stimulate the respiratory burst. These results not only define a novel mechanism through which some of the actions of arachidonic acid are mediated but also demonstrate that, in addition to ErbB1 (epidermal growth factor receptor), ErbB4 can also be transactivated by a non-epidermal growth factor-like ligand.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				F. A. Yaghini, F. Li, and K. U. Malik Expression and Mechanism of Spleen Tyrosine Kinase Activation by Angiotensin II and Its Implication in Protein Synthesis in Rat Vascular Smooth Muscle Cells J. Biol. Chem., June 8, 2007; 282(23): 16878 - 16890. [Abstract] [Full Text] [PDF]

				C. Zheng, Z. Lin, Z. J. Zhao, Y. Yang, H. Niu, and X. Shen MAPK-activated Protein Kinase-2 (MK2)-mediated Formation and Phosphorylation-regulated Dissociation of the Signal Complex Consisting of p38, MK2, Akt, and Hsp27 J. Biol. Chem., December 1, 2006; 281(48): 37215 - 37226. [Abstract] [Full Text] [PDF]

				C. Kim and M. C. Dinauer Impaired NADPH oxidase activity in Rac2-deficient murine neutrophils does not result from defective translocation of p47phox and p67phox and can be rescued by exogenous arachidonic acid J. Leukoc. Biol., January 1, 2006; 79(1): 223 - 234. [Abstract] [Full Text] [PDF]

				C. S. Hii, D. S. Anson, M. Costabile, V. Mukaro, K. Dunning, and A. Ferrante Characterization of the MEK5-ERK5 Module in Human Neutrophils and Its Relationship to ERK1/ERK2 in the Chemotactic Response J. Biol. Chem., November 26, 2004; 279(48): 49825 - 49834. [Abstract] [Full Text] [PDF]

				Y. I. Miller, D. S. Worrall, C. D. Funk, J. R. Feramisco, and J. L. Witztum Actin Polymerization in Macrophages in Response to Oxidized LDL and Apoptotic Cells: Role of 12/15-Lipoxygenase and Phosphoinositide 3-Kinase Mol. Biol. Cell, October 1, 2003; 14(10): 4196 - 4206. [Abstract] [Full Text] [PDF]

				B.-S. Li, W. Ma, H. Jaffe, Y. Zheng, S. Takahashi, L. Zhang, A. B. Kulkarni, and H. C. Pant Cyclin-dependent Kinase-5 Is Involved in Neuregulin-dependent Activation of Phosphatidylinositol 3-Kinase and Akt Activity Mediating Neuronal Survival J. Biol. Chem., September 12, 2003; 278(37): 35702 - 35709. [Abstract] [Full Text] [PDF]

				J. Liu, Z. Liu, S. Chuai, and X. Shen Phospholipase C and phosphatidylinositol 3-kinase signaling are involved in the exogenous arachidonic acid-stimulated respiratory burst in human neutrophils J. Leukoc. Biol., September 1, 2003; 74(3): 428 - 437. [Abstract] [Full Text] [PDF]

				N. Moghaddami, M. Costabile, P. K. Grover, H. P. A. Jersmann, Z. H. Huang, C. S. T. Hii, and A. Ferrante Unique Effect of Arachidonic Acid on Human Neutrophil TNF Receptor Expression: Up-Regulation Involving Protein Kinase C, Extracellular Signal-Regulated Kinase, and Phospholipase A2 J. Immunol., September 1, 2003; 171(5): 2616 - 2624. [Abstract] [Full Text] [PDF]

				L. A. deGraffenried, W. E. Friedrichs, L. Fulcher, G. Fernandes, J. M. Silva, J.-M. Peralba, and M. Hidalgo Eicosapentaenoic acid restores tamoxifen sensitivity in breast cancer cells with high Akt activity Ann. Onc., July 1, 2003; 14(7): 1051 - 1056. [Abstract] [Full Text] [PDF]

				S. Grenier, N. Flamand, J. Pelletier, P. H. Naccache, P. Borgeat, and S. G. Bourgoin Arachidonic acid activates phospholipase D in human neutrophils; essential role of endogenous leukotriene B4 and inhibition by adenosine A2A receptor engagement J. Leukoc. Biol., April 1, 2003; 73(4): 530 - 539. [Abstract] [Full Text] [PDF]

				E. Burkert, D. Szellas, O. Radmark, D. Steinhilber, and O. Werz Cell type-dependent activation of 5-lipoxygenase by arachidonic acid J. Leukoc. Biol., January 1, 2003; 73(1): 191 - 200. [Abstract] [Full Text] [PDF]

				R. Kettritz, M. Choi, W. Butt, M. Rane, S. Rolle, F. C. Luft, and J. B. Klein Phosphatidylinositol 3-Kinase Controls Antineutrophil Cytoplasmic Antibodies--Induced Respiratory Burst in Human Neutrophils J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1740 - 1749. [Abstract] [Full Text] [PDF]