The Cyclosporin A-sensitive Nuclear Factor of Activated T Cells (NFAT) Proteins Are Expressed in Vascular Smooth Muscle Cells DIFFERENTIAL LOCALIZATION OF NFAT ISOFORMS AND INDUCTION OF NFAT-MEDIATED TRANSCRIPTION BY PHOSPHOLIPASE C-COUPLED CELL SURFACE RE

来自 NCBI

喜欢 0

阅读量：

105

作者：

V Boss，KL Abbott，XF Wang，GK Pavlath，TJ Murphy

展开

摘要：

Expression of the antigen-regulated, cyclosporin A-sensitive nuclear factor of activated T cells (NFAT) is not restricted to lymphoid cells, as thought initially, but the physiological inducers of NFAT-mediated transcription in non-lymphoid cells are unknown. Here, cultured vascular smooth muscle cells (VSMC) are shown to express two isoforms of the NFAT family endogenously, which are localized differentially in cells under resting conditions. Using a retroviral NFAT-specific luciferase reporter, we show that VSMC support previously unrecognized complexities in NFAT-mediated transcription, including evidence for negative regulation by Casignaling and positive regulation through co-activation of adenylyl cyclase and Camobilization. The VSMC mitogen platelet derived growth factor-BB (PDGF-BB) induces NFAT-mediated transcription in VSMC. Thrombin and angiotensin II, which activate Gα-coupled receptors, are significantly weaker inducers of NFAT-mediated luciferase expression than is PDGF-BB. However, co-stimulation studies show that Gαreceptor agonists augment the NFAT-mediated transcriptional response to PDGF-BB. This synergy can be explained in part by augmented intracellular Catransients elicited by multiple agonist challenges. These data indicate that agonists for phospholipase C-coupled receptors stimulate NFAT-mediated transcription in VSMC differentially, and that NFAT can function to integrate co-activating signals in the extracellular environment.

展开

关键词：

Animals Rats T-Lymphocytes Cells, Cultured Calcium Cyclosporine Tetradecanoylphorbol Acetate GTP-Binding Proteins Thrombin Transcription Factors