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

J. Biol. Chem., Vol. 279, Issue 20, 21085-21095, May 14, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/20/21085    most recent M400063200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gardai, S. J. Articles by Henson, P. M. Search for Related Content PubMed PubMed Citation Articles by Gardai, S. J. Articles by Henson, P. M. Social Bookmarking                      What's this?

xPhosphorylation of Bax Ser¹⁸⁴ by Akt Regulates Its Activity and Apoptosis in Neutrophils^*

Shyra J. Gardai, David A. Hildeman¶, Steve K. Frankel||, Ben B. Whitlock**, S. Courtney Frasch, Niels Borregaard, Philippa Marrack, Donna L. Bratton, and Peter M. Henson¶¶

From the Program in Cell Biology, Department of Pediatrics, and the Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado 80206, the Departments of Pathology and ^||Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, the ^¶Department of Immunobiology, Cincinnati Children's Hospital, Cincinnati, Ohio 45229, the ^**Department of Biology, West Virginia Wesleyan College, Buckhannon, West Virginia 26201, and the Department of Hematology, Finsen Center, National University Hosptial, Rigshospitalet, 9 Blegdamsvej, 2100 Copenhagen, Denmark

Although important for apoptosis, the mechanism of Bax regulation is poorly understood. This study demonstrates that phosphorylation of Ser¹⁸⁴ regulates Bax activity. The phosphorylation required phosphatidylinositol 3-kinase/Akt activation and appeared to be mediated by Akt itself. In the serine-phosphorylated form, Bax was detected in the cytoplasm, could not be immunoprecipitated with the activation-specific antibody 6A7, and promoted heterodimerization with Mcl-1, Bcl-x_L, and A1. Apoptotic neutrophils possessed reduced levels of serine-phosphorylated Bax correlating with an increase in activated Bax as well as an increase in the amount of Bax found translocated to the mitochondria. We suggest that Bax is regulated by phosphorylation of Ser¹⁸⁴ in an Akt-dependent manner and that phosphorylation inhibits Bax effects on the mitochondria by maintaining the protein in the cytoplasm, heterodimerized with antiapoptotic Bcl-2 family members.

Received for publication, January 5, 2004 , and in revised form, February 3, 2004.

^* 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: National Jewish Medical and Research Center, D508, 1400 Jackson St., Denver, CO 80206. Tel.: 303-398-1380; Fax: 303-398-1381; E-mail: hensonp{at}NJC.org.

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

This article has been cited by other articles:

				A. Havasi, Z. Li, Z. Wang, J. L. Martin, V. Botla, K. Ruchalski, J. H. Schwartz, and S. C. Borkan Hsp27 Inhibits Bax Activation and Apoptosis via a Phosphatidylinositol 3-Kinase-dependent Mechanism J. Biol. Chem., May 2, 2008; 283(18): 12305 - 12313. [Abstract] [Full Text] [PDF]

				H. Arokium, H. Ouerfelli, G. Velours, N. Camougrand, F. M. Vallette, and S. Manon Substitutions of Potentially Phosphorylatable Serine Residues of Bax Reveal How They May Regulate Its Interaction with Mitochondria J. Biol. Chem., November 30, 2007; 282(48): 35104 - 35112. [Abstract] [Full Text] [PDF]

				G. Sheng, J. Guo, and B. W. Warner Epidermal growth factor receptor signaling modulates apoptosis via p38{alpha} MAPK-dependent activation of Bax in intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, September 1, 2007; 293(3): G599 - G606. [Abstract] [Full Text] [PDF]

				M. Xin, F. Gao, W. S. May, T. Flagg, and X. Deng Protein Kinase C{zeta} Abrogates the Proapoptotic Function of Bax through Phosphorylation J. Biol. Chem., July 20, 2007; 282(29): 21268 - 21277. [Abstract] [Full Text] [PDF]

				R. Blomgran, L. Zheng, and O. Stendahl Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization J. Leukoc. Biol., May 1, 2007; 81(5): 1213 - 1223. [Abstract] [Full Text] [PDF]

				S. A. Trushin, A. Algeciras-Schimnich, S. R. Vlahakis, G. D. Bren, S. Warren, D. J. Schnepple, and A. D. Badley Glycoprotein 120 Binding to CXCR4 Causes p38-Dependent Primary T Cell Death That Is Facilitated by, but Does Not Require Cell-Associated CD4 J. Immunol., April 15, 2007; 178(8): 4846 - 4853. [Abstract] [Full Text] [PDF]

				L. Yang, M. Sun, X.-m. Sun, G. Z. Cheng, S. V. Nicosia, and J. Q. Cheng Akt Attenuation of the Serine Protease Activity of HtrA2/Omi through Phosphorylation of Serine 212 J. Biol. Chem., April 13, 2007; 282(15): 10981 - 10987. [Abstract] [Full Text] [PDF]

				B.-J. Kim, S.-W. Ryu, and B.-J. Song JNK- and p38 Kinase-mediated Phosphorylation of Bax Leads to Its Activation and Mitochondrial Translocation and to Apoptosis of Human Hepatoma HepG2 Cells J. Biol. Chem., July 28, 2006; 281(30): 21256 - 21265. [Abstract] [Full Text] [PDF]

				M. Xin and X. Deng Protein Phosphatase 2A Enhances the Proapoptotic Function of Bax through Dephosphorylation J. Biol. Chem., July 7, 2006; 281(27): 18859 - 18867. [Abstract] [Full Text] [PDF]

				K. Ruchalski, H. Mao, Z. Li, Z. Wang, S. Gillers, Y. Wang, D. D. Mosser, V. Gabai, J. H. Schwartz, and S. C. Borkan Distinct hsp70 Domains Mediate Apoptosis-inducing Factor Release and Nuclear Accumulation J. Biol. Chem., March 24, 2006; 281(12): 7873 - 7880. [Abstract] [Full Text] [PDF]

				A. B. Alvero, W. Chen, A. C. Sartorelli, P. Schwartz, T. Rutherford, and G. Mor Triapine (3-aninopyridine-2-carboxaldehyde thiosemicarbazone) Induces Apoptosis in Ovarian Cancer Cells Reproductive Sciences, February 1, 2006; 13(2): 145 - 152. [Abstract] [PDF]

				M. Xin and X. Deng Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation J. Biol. Chem., March 18, 2005; 280(11): 10781 - 10789. [Abstract] [Full Text] [PDF]

				H. Arokium, N. Camougrand, F. M. Vallette, and S. Manon Studies of the Interaction of Substituted Mutants of BAX with Yeast Mitochondria Reveal That the C-terminal Hydrophobic {alpha}-Helix Is a Second ART Sequence and Plays a Role in the Interaction with Anti-apoptotic BCL-xL J. Biol. Chem., December 10, 2004; 279(50): 52566 - 52573. [Abstract] [Full Text] [PDF]

				N. Parikh, H. Sade, L. Kurian, and A. Sarin The Bax N Terminus Is Required for Negative Regulation by the Mitogen-Activated Protein Kinase Kinase and Akt Signaling Pathways in T Cells J. Immunol., November 15, 2004; 173(10): 6220 - 6227. [Abstract] [Full Text] [PDF]

				D. A. Linseman, B. D. Butts, T. A. Precht, R. A. Phelps, S. S. Le, T. A. Laessig, R. J. Bouchard, M. L. Florez-McClure, and K. A. Heidenreich Glycogen Synthase Kinase-3{beta} Phosphorylates Bax and Promotes Its Mitochondrial Localization during Neuronal Apoptosis J. Neurosci., November 3, 2004; 24(44): 9993 - 10002. [Abstract] [Full Text] [PDF]