The Journal of Immunology, Vol 157, Issue 1 146-155, Copyright © 1996 by American Association of Immunologists

ARTICLES

Transcriptional regulation of the junB promoter in mature B lymphocytes. Activation through a cyclic adenosine 3',5'-monophosphate- like binding site

SF Amato, K Nakajima, T Hirano and TC Chiles
Department of Biology, Boston College, Chestnut Hill, MA 02167, USA.

The experiments presented herein were designed to understand the molecular mechanism(s) by which membrane Ig (mIg)-dependent signals are integrated at the level of the junB promoter to induce gene transcription. Functional studies using chloramphenicol acetyltransferase reporter gene constructs that contained deleted 5' flanking region junB sequences identified a region located between -194 and -87 that contains an Ets binding site and a putative cAMP response element binding site (CRE-like). Point mutagenesis of the CRE-like site blocked junB promoter activation in response to mIg cross-linking in mature Bal17 B cells. Nuclear extract binding activity to a synthetic oligonucleotide containing the junB CRE-like site was detected in unstimulated B cells and was increased in response to mIg cross- linking. Binding activity was competed with unlabeled oligonucleotides that contained the junB CRE-like site or the somatostatin CRE consensus motif, the latter observation suggests that members of the activating transcription factor/CRE binding protein (CREB) family may mediate mIg- dependent junB transcription. Consistent with this interpretation, recombinant CREB and activating transcription factor proteins bound the junB CRE-like site, but did not interact with a mutant CRE-like site. Expression of a dominant negative CREB protein blocked mIg-mediated transcription from a junB CRE-like site-chloramphenicol acetyltransferase reporter gene. CRE-like nucleoprotein complexes from Bal17 B cells contained constitutively bound CREB-1, which was phosphorylated on serine 133 in response to mIg cross-linking. Activating transcription factor-1 protein was also constitutively expressed in CRE-like nucleoprotein complexes. Collectively, these results suggest that components of the protein kinase A signaling pathway are recruited by mIg to induce junB transcription.

This article has been cited by other articles:

				H.-C. Chen, J. C. Byrd, and N. Muthusamy Differential Role for Cyclic AMP Response Element Binding Protein-1 in Multiple Stages of B Cell Development, Differentiation, and Survival J. Immunol., February 15, 2006; 176(4): 2208 - 2218. [Abstract] [Full Text] [PDF]

				J. T. Blois, J. M. Mataraza, I. Mecklenbrauker, A. Tarakhovsky, and T. C. Chiles B Cell Receptor-induced cAMP-response Element-binding Protein Activation in B Lymphocytes Requires Novel Protein Kinase C{delta} J. Biol. Chem., July 16, 2004; 279(29): 30123 - 30132. [Abstract] [Full Text] [PDF]

				G. R. Wiggin, A. Soloaga, J. M. Foster, V. Murray-Tait, P. Cohen, and J. S. C. Arthur MSK1 and MSK2 Are Required for the Mitogen- and Stress-Induced Phosphorylation of CREB and ATF1 in Fibroblasts Mol. Cell. Biol., April 15, 2002; 22(8): 2871 - 2881. [Abstract] [Full Text] [PDF]

				J. M. Swart, D. M. Bergeron, and T. C. Chiles Identification of a Membrane Ig-Induced p38 Mitogen-Activated Protein Kinase Module That Regulates cAMP Response Element Binding Protein Phosphorylation and Transcriptional Activation in CH31 B Cell Lymphomas J. Immunol., March 1, 2000; 164(5): 2311 - 2319. [Abstract] [Full Text] [PDF]

				K. Obrietan, S. Impey, D. Smith, J. Athos, and D. R. Storm Circadian Regulation of cAMP Response Element-mediated Gene Expression in the Suprachiasmatic Nuclei J. Biol. Chem., June 18, 1999; 274(25): 17748 - 17756. [Abstract] [Full Text] [PDF]

				M. Fujihara, K. Ikebuchi, T. L. Maekawa, S. Wakamoto, C. Ogiso, T. Ito, T. A. Takahashi, T. Suzuki, and S. Sekiguchi Lipopolysaccharide-Induced Desensitization of junB Gene Expression in a Mouse Macrophage-Like Cell Line, P388D1 J. Immunol., October 1, 1998; 161(7): 3659 - 3665. [Abstract] [Full Text] [PDF]

				D.-H. Zhang, L. Cohn, P. Ray, K. Bottomly, and A. Ray Transcription Factor GATA-3 Is Differentially Expressed in Murine Th1 and Th2 Cells and Controls Th2-specific Expression of the Interleukin-5 Gene J. Biol. Chem., August 22, 1997; 272(34): 21597 - 21603. [Abstract] [Full Text] [PDF]