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  • Title: Induction of CREB activity via the surface Ig receptor of B cells.
    Author: Xie H, Chiles TC, Rothstein TL.
    Journal: J Immunol; 1993 Jul 15; 151(2):880-9. PubMed ID: 8393039.
    Abstract:
    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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