Huggenvik J I, Collard M W, Kim Y W, Sharma R P
Center for Environmental Toxicology, Utah State University, Logan 84322-5600.
Mol Endocrinol. 1993 Apr;7(4):543-50. doi: 10.1210/mend.7.4.8388997.
Retinoic acid receptors (RARs) are ligand-activated nuclear transcription factors that belong to the steroid-thyroid hormone receptor superfamily. We have used the transient transfection of a retinoic acid-responsive reporter plasmid (RARECAT) to investigate the potential interactions between the retinoic acid (RA) and cAMP signaling pathways. Cotransfections of expression plasmids for the catalytic (C) subunits of cAMP-dependent protein kinase with RARECAT showed ligand-independent activation in both CV-1 and HeLa cells and a further 2-fold increase in RARECAT activity in the presence of RA. In CV-1 cells, cotransfections of the expression plasmids for RAR and the C-subunits produced increases in RARECAT activity (12- and 8-fold in the absence of ligand and 21- and 15-fold in the presence of RA for the C alpha- and C beta-isoforms, respectively). Cotransfections of both the C beta-subunit and RAR expression plasmids in HeLa cells produced 22- and 114-fold increases in RARECAT activity in the absence and presence of RA, respectively. These results provide evidence to suggest that the RA and cAMP signaling pathways are coupled, and signaling cross-talk may occur through the direct phosphorylation of RARs by the C-subunit as indicated by in vitro phosphorylation of the receptor.
维甲酸受体（RARs）是配体激活的核转录因子，属于类固醇-甲状腺激素受体超家族。我们利用维甲酸反应性报告质粒（RARECAT）的瞬时转染来研究维甲酸（RA）和cAMP信号通路之间的潜在相互作用。将cAMP依赖性蛋白激酶催化（C）亚基的表达质粒与RARECAT共转染，在CV-1和HeLa细胞中均显示出不依赖配体的激活，并且在存在RA的情况下RARECAT活性进一步增加2倍。在CV-1细胞中，RAR和C亚基的表达质粒共转染使RARECAT活性增加（对于Cα和Cβ同工型，在无配体时分别增加12倍和8倍，在存在RA时分别增加21倍和15倍）。在HeLa细胞中，Cβ亚基和RAR表达质粒的共转染在无RA和有RA时分别使RARECAT活性增加22倍和114倍。这些结果提供了证据表明RA和cAMP信号通路是偶联的，并且如受体的体外磷酸化所示，信号转导可能通过C亚基对RAR的直接磷酸化而发生。
