Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ Scotland, United Kingdom.
Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ Scotland, United Kingdom.
FEBS Lett. 2014 May 2;588(9):1556-61. doi: 10.1016/j.febslet.2014.02.038. Epub 2014 Mar 11.
The cyclic AMP sensor, EPAC1, activates AP1-mediated transcription in HUVECs. Correspondingly, induction of the SOCS3 minimal promoter by EPAC1 requires a single AP1 site that constitutively binds phosphorylated (Ser63) c-Jun in DNA-pull-down assays. c-Jun (Ser63) becomes further phosphorylated following cyclic AMP stimulation and specific activation of protein kinase A (PKA), but not through selective activation of EPAC1. Moreover, despite a requirement for c-Jun for SOCS3 induction in fibroblasts, phospho-null c-Jun (Ser63/73Ala) had little effect on SOCS3 induction by cyclic AMP in HUVECs. AP1 activation and SOCS3 induction by EPAC1 in HUVECs therefore occur independently of c-Jun phosphorylation on Ser63.
环腺苷酸传感器 EPAC1 激活 HUVECs 中的 AP1 介导的转录。相应地，EPAC1 诱导 SOCS3 最小启动子需要一个单个的 AP1 位点，该位点在 DNA 下拉实验中持续结合磷酸化（Ser63）的 c-Jun。c-Jun（Ser63）在环 AMP 刺激和蛋白激酶 A（PKA）的特异性激活后进一步磷酸化，但不是通过 EPAC1 的选择性激活。此外，尽管 c-Jun 是成纤维细胞中 SOCS3 诱导所必需的，但磷酸化缺失的 c-Jun（Ser63/73Ala）对 HUVECs 中环 AMP 诱导的 SOCS3 诱导几乎没有影响。因此，EPAC1 在 HUVECs 中对 AP1 的激活和 SOCS3 的诱导独立于 c-Jun 的 Ser63 磷酸化。
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