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Zhihui Xie, Eric N Johnson, Kirk M Druey, Rgs13 acts as a nuclear repressor of CREB in B lymphocytes (B10), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page LB2, https://doi.org/10.4049/jimmunol.178.Supp.B10
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Abstract
The autonomic nervous system profoundly impacts immune functions, particularly during stress. Norepinephrine stimulates Gαs-coupled β2-adrenergic receptors on B lymphocytes, leading to cAMP response element binding protein (CREB)-mediated transcription of a variety of genes including the B-cell specific Oct 2 coactivator (OCA-B). Regulator of G protein signaling 13 (Rgs13) is a member of a large protein family that attenuates G-protein-mediated signal transduction by acting as GTPase-accelerating-proteins (GAPs) for Gαi and Gαq but not Gαs. Here, we show that Rgs13, which is enriched in germinal center B lymphocytes, is a direct transcriptional repressor of CREB in B cells. OCA-B expression is increased in B cells from Rgs13−/− mice both in the basal state and after exposure to the β2-agonist terbutaline in vitro. β2-adrenergic receptor stimulation induces nuclear translocation of Rgs13 and binding to activated pCREB in a complex with CREB binding protein (CBP/p300). This interaction impairs CREB binding to DNA and transcription of a CRE reporter gene. Rgs13 −/− B lymphocytes exhibit increased basal and agonist-stimulated pCREB-DNA binding. We propose that Rgs13 acts as a direct nuclear inhibitor of CREB-driven transcription in B lymphocytes independent of its GAP activity. As a result, Rgs13 may mediate important aspects of neural regulation of humoral immune responses.
