Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation and function of CREB was examined in B cells to begin to elucidate the role of cAMP-derived signals in B cell activation. CRE-binding activity detected by the electrophoretic mobility shift assay was found to be constitutively expressed in nuclear extracts of primary murine splenic B cells and was unchanged in nuclear extracts obtained from B cells stimulated in a variety of ways. This activity was shown to be specific by competition analysis and to represent CREB or a closely related molecule on the basis of a "supershift" in the mobility of the nucleoprotein complex induced by anti-CREB antiserum. The function of B cell CREB was assessed by transient transfection of the murine B lymphoma cell line, BAL-17, with a CRE-dependent chloramphenicol acetyl-transferase (CAT) construct that contains a portion of the somatostatin promoter. Cross-linking of the surface Ig receptors of transfected BAL-17 B cells produced a threefold induction of CAT activity. Forskolin, which markedly induced CAT expression in PC12 cells transfected with the CRE-dependent construct, failed to stimulate CAT activity in transfected BAL-17 B cells despite an increase in cAMP. However, anti-Ig was found to act in synergy with forskolin to produce enhanced CAT activity. A phosphoprotein of appropriate molecular size for CREB was immunoprecipitated from anti-Ig plus forskolin treated BAL-17 B cells. These results suggest that CREB is present in primary B cells and that CRE-dependent gene expression is regulated by surface Ig either alone or in synergy with cAMP; the latter implies cross-talk between intracellular signaling pathways acting at the level of CREB.
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PMID:Induction of CREB activity via the surface Ig receptor of B cells. 839 39

We previously reported that cross-linking surface immunoglobulin (sIg) leads to induction of the transcription factor CREB in B lymphocytes through phosphorylation at Ser133, despite the lack of an increase in cAMP. Further, cAMP-raising agents fail to induce CREB Ser133 phosphorylation and CRE-dependent gene expression in these cells, which differs sharply from the situation in PC12 rat pheochromocytoma cells where CREB responds to elevation of cAMP through the activity of protein kinase A. In this study, we characterized the signal transduction pathways leading from sIg engagement to CREB activation. By using specific inhibitors for protein kinase C (PKC), Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), and protein kinase A (PKA), we found that anti-Ig-induced CREB Ser133 phosphorylation depends on PKC, but does not require activation of PKA or CaM kinase II. The differential responsiveness of CREB to forskolin in PC12 cells and BAL-17 B cells may relate to the more marked elevation of cAMP in the former as opposed to the latter; however, high concentrations of dbcAMP which should readily enter B cells and artificially increase cAMP levels still failed to induce CREB Ser133 phosphorylation, even in conjunction with a phosphodiesterase inhibitor. Taken together, the cAMP/PKA pathway does not appear to be as active a contributor to CREB phosphorylation in B lymphocytes as in PC12 cells, and does not appear to be involved in sIg-induced, PKC-dependent, CREB activation.
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PMID:Signaling pathways for antigen receptor-mediated induction of transcription factor CREB in B lymphocytes. 862 May 54

Engagement of surface immunoglobulin on mature B cells leads to rescue from apoptosis and to proliferation. Levels of bcl-2 mRNA and protein increase with cross-linking of surface immunoglobulin. We have located the major positive regulatory region for control of bcl-2 expression in B cells in the 5'-flanking region. The positive region can be divided into an upstream and a downstream regulatory region. The downstream regulatory region contains a cyclic AMP-responsive element (CRE). We show by antibody supershift experiments and UV cross-linking followed by denaturing polyacrylamide gel electrophoresis that both CREB and ATF family members bind to this region in vitro. Mutations of the CRE site that result in loss of CREB binding also lead to loss of functional activity of the bcl-2 promoter in transient-transfection assays. The presence of an active CRE site in the bcl-2 promoter implies that the regulation of bcl-2 expression is linked to a signal transduction pathway in B cells. Treatment of the mature B-cell line BAL-17 with either anti-immunoglobulin M or phorbol 12-myristate 13-acetate leads to an increase in bcl-2 expression that is mediated by the CRE site. Treatment of the more immature B-cell line, Ramos, with phorbol esters rescues the cells from calcium-dependent apoptosis. bcl-2 expression is increased following phorbol ester treatment, and the increased expression is dependent on the CRE site. These stimuli result in phosphorylation of CREB at serine 133. The phosphorylation of CREB that results in activation is mediated by protein kinase C rather than by protein kinase A. Although the CRE site is necessary, optimal induction of bcl-2 expression requires participation of the upstream regulatory element, suggesting that phosphorylation of CREB alters its interaction with the upstream regulatory element. The CRE site in the bcl-2 promoter appears to play a major role in the induction of bcl-2 expression during the activation of mature B cells and during the rescue of immature B cells from apoptosis. It is possible that the CRE site is responsible for induction of bcl-2 expression in other cell types, particularly those in which protein kinase C is involved.
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PMID:Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis. 881 67