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

J. Biol. Chem., Vol. 280, Issue 41, 34538-34547, October 14, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/41/34538    most recent M504943200v1 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 Sasaki, C. Y. Articles by Longo, D. L. Search for Related Content PubMed PubMed Citation Articles by Sasaki, C. Y. Articles by Longo, D. L. Social Bookmarking                      What's this?

Phosphorylation of RelA/p65 on Serine 536 Defines an IB-independent NF-B Pathway^*

From the Laboratory of Immunology, NIA, National Institutes of Health, Baltimore, Maryland 21224

The association of the NF-B p65/p50 dimer with IB plays a pivotal role in regulating its nuclear translocation and gene transcription. In addition, serine phosphorylation at various sites of the p65 subunit has been shown to be important in initiating transcription. Here we demonstrate that the regulation of nuclear translocation of p65 phosphorylated at serine 536 is not dependent on IB. Stimulation of either Jurkat or normal human T cells resulted in the nuclear translocation of phospho-p65 (Ser⁵³⁶). In addition, the phospho-p65 (Ser⁵³⁶) was not associated with either IB or p50, and the nuclear translocation of phospho-p65 (Ser⁵³⁶), but not total p65, was unaffected by the proteosome inhibitor MG-132, which blocks IB protein degradation and prevents p65/p50 dimer nuclear translocation. Accordingly, the co-expression of a dominant negative mutant of IB blocked the transcriptional activity mediated by wild type but not the dominant positive p65 mutant (S536D). Furthermore, the transfection of the S536D form of p65 led to the induction of interleukin-8 transcription following stimulation, whereas the S536A form, which cannot be phosphorylated at this site, did not. Together, the findings suggest that p65 phosphorylated on serine 536 is not associated with or regulated by IB, that it has a distinct set of target genes, and that it may represent a noncanonical NF-B pathway that is independent of IB regulation.

Received for publication, May 4, 2005 , and in revised form, August 11, 2005.

^* 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.

¹ To whom correspondence should be addressed: Laboratory of Immunology, National Institute on Aging, 5600 Nathan Shock Dr., Baltimore, MD 21224. Tel.: 410-558-8096; Fax: 410-558-8284; E-mail: sasakic{at}grc.nia.nih.gov.

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

This article has been cited by other articles:

				R. Sitcheran, W. C. Comb, P. C. Cogswell, and A. S. Baldwin Essential Role for Epidermal Growth Factor Receptor in Glutamate Receptor Signaling to NF-{kappa}B Mol. Cell. Biol., August 15, 2008; 28(16): 5061 - 5070. [Abstract] [Full Text] [PDF]

				H. Gutierrez, G. W. O'Keeffe, N. Gavalda, D. Gallagher, and A. M. Davies Nuclear Factor {kappa}B Signaling Either Stimulates or Inhibits Neurite Growth Depending on the Phosphorylation Status of p65/RelA J. Neurosci., August 13, 2008; 28(33): 8246 - 8256. [Abstract] [Full Text] [PDF]

				K. Fink, A. Duval, A. Martel, A. Soucy-Faulkner, and N. Grandvaux Dual Role of NOX2 in Respiratory Syncytial Virus- and Sendai Virus-Induced Activation of NF-{kappa}B in Airway Epithelial Cells J. Immunol., May 15, 2008; 180(10): 6911 - 6922. [Abstract] [Full Text] [PDF]

				C. L. Bristow, R. Wolkowicz, M. Trucy, A. Franklin, F. Di Meo, M. T. Kozlowski, R. Winston, and R. R. Arnold NF-{kappa}B Signaling, Elastase Localization, and Phagocytosis Differ in HIV-1 Permissive and Nonpermissive U937 Clones J. Immunol., January 1, 2008; 180(1): 492 - 499. [Abstract] [Full Text] [PDF]

				C. Y. Sasaki, C. F. Slemenda, P. Ghosh, T. J. Barberi, and D. L. Longo Traf1 Induction and Protection from Tumor Necrosis Factor by Nuclear Factor-{kappa}B p65 Is Independent of Serine 536 Phosphorylation Cancer Res., December 1, 2007; 67(23): 11218 - 11225. [Abstract] [Full Text] [PDF]

				N. El Mjiyad, S. Bontems, G. Gloire, J. Horion, P. Vandevenne, E. Dejardin, J. Piette, and C. Sadzot-Delvaux Varicella-Zoster Virus Modulates NF-{kappa}B Recruitment on Selected Cellular Promoters J. Virol., December 1, 2007; 81(23): 13092 - 13104. [Abstract] [Full Text] [PDF]

				C. Nicholas, S. Batra, M. A. Vargo, O. H. Voss, M. A. Gavrilin, M. D. Wewers, D. C. Guttridge, E. Grotewold, and A. I. Doseff Apigenin Blocks Lipopolysaccharide-Induced Lethality In Vivo and Proinflammatory Cytokines Expression by Inactivating NF-{kappa}B through the Suppression of p65 Phosphorylation J. Immunol., November 15, 2007; 179(10): 7121 - 7127. [Abstract] [Full Text] [PDF]

				J. Partridge, H. Carlsen, K. Enesa, H. Chaudhury, M. Zakkar, L. Luong, A. Kinderlerer, M. Johns, R. Blomhoff, J. C. Mason, et al. Laminar shear stress acts as a switch to regulate divergent functions of NF-{kappa}B in endothelial cells FASEB J, November 1, 2007; 21(13): 3553 - 3561. [Abstract] [Full Text] [PDF]

				S. Choudhary, M. Lu, R. Cui, and A. R. Brasier Involvement of a Novel Rac/RhoA Guanosine Triphosphatase-Nuclear Factor-{kappa}B Inducing Kinase Signaling Pathway Mediating Angiotensin II-Induced RelA Transactivation Mol. Endocrinol., September 1, 2007; 21(9): 2203 - 2217. [Abstract] [Full Text] [PDF]

				M. Neumann and M. Naumann Beyond I{kappa}Bs: alternative regulation of NF-{kappa}B activity FASEB J, September 1, 2007; 21(11): 2642 - 2654. [Abstract] [Full Text] [PDF]

				W. W. Polk, M. E. Ellis, J. V. Kushleika, P. L. Simmonds, and J. S. Woods RhoA regulation of NF-{kappa}B activation is mediated by COX-2-dependent feedback inhibition of IKK in kidney epithelial cells Am J Physiol Cell Physiol, September 1, 2007; 293(3): C1160 - C1170. [Abstract] [Full Text] [PDF]

				P. Mandrekar, V. Jeliazkova, D. Catalano, and G. Szabo Acute Alcohol Exposure Exerts Anti-Inflammatory Effects by Inhibiting I{kappa}B Kinase Activity and p65 Phosphorylation in Human Monocytes J. Immunol., June 15, 2007; 178(12): 7686 - 7693. [Abstract] [Full Text] [PDF]

				S. Skvortsov, I. Skvortsova, T. Stasyk, N. Schiefermeier, A. Neher, A. R. Gunkel, G. K. Bonn, L. A. Huber, P. Lukas, C. M. Pleiman, et al. Antitumor activity of CTFB, a novel anticancer agent, is associated with the down-regulation of nuclear factor-{kappa}B expression and proteasome activation in head and neck squamous carcinoma cell lines Mol. Cancer Ther., June 1, 2007; 6(6): 1898 - 1908. [Abstract] [Full Text] [PDF]

				P. Liu, M. Jamaluddin, K. Li, R. P. Garofalo, A. Casola, and A. R. Brasier Retinoic Acid-Inducible Gene I Mediates Early Antiviral Response and Toll-Like Receptor 3 Expression in Respiratory Syncytial Virus-Infected Airway Epithelial Cells J. Virol., February 1, 2007; 81(3): 1401 - 1411. [Abstract] [Full Text] [PDF]

				K. M. Wilczynska, S. M. Gopalan, M. Bugno, A. Kasza, B. S. Konik, L. Bryan, S. Wright, I. Griswold-Prenner, and T. Kordula A Novel Mechanism of Tissue Inhibitor of Metalloproteinases-1 Activation by Interleukin-1 in Primary Human Astrocytes J. Biol. Chem., November 17, 2006; 281(46): 34955 - 34964. [Abstract] [Full Text] [PDF]

				D. Hargett, S. Rice, and S. L. Bachenheimer Herpes Simplex Virus Type 1 ICP27-Dependent Activation of NF-{kappa}B J. Virol., November 1, 2006; 80(21): 10565 - 10578. [Abstract] [Full Text] [PDF]

				Y.-J. Song, K.-Y. Jen, V. Soni, E. Kieff, and E. Cahir-McFarland IL-1 receptor-associated kinase 1 is critical for latent membrane protein 1-induced p65/RelA serine 536 phosphorylation and NF-{kappa}B activation PNAS, February 21, 2006; 103(8): 2689 - 2694. [Abstract] [Full Text] [PDF]