PLCγ2 activates CREB-dependent transcription in PC12 cells through phosphorylation of CREB at Serine 133
PLCγ2 activates CREB-dependent transcription in PC12 cells through phosphorylation of CREB at Serine 133
复制标题
DOI：
10.1007/s10616-005-3763-6
复制
发表时间：
2005-01-01
期刊：
影响因子：
2.2
通讯作者：
Kida, S
中科院分区：
文献类型：
--
作者：
Iwamoto, T;Mamiya, N;Kida, S
cAMP和Ca2+信号通路通过其在丝氨酸133处的磷酸化激活转录因子CREB。CREB的激活参与各种生物现象的调节。为了进一步了解CREB活性响应cAMP和Ca 2+信号通路激活的调节机制，我们研究了PLC γ在PC 12细胞中CREB激活中的作用。siRNA介导的PLC γ 2表达的减少，而不是PLC γ 1，抑制CREB在S133的磷酸化和CREB依赖性转录的激活后，用毛喉素或离子霉素处理细胞，分别增加cAMP或Ca2+的细胞内浓度。重要的是，靶向PLC γ 2的siRNA通过Ca2+信号而不是cAMP信号完全消除了CREB激活。这些结果表明，PLC γ 2作为一个重要的信号转导，导致CREB激活响应激活的Ca 2+信号通路，cAMP信号通路可能通过磷酸化CREB的PKA和PLC γ 2介导的另一个信号通路激活CREB。
The cAMP and Ca2+ signaling pathways activate the transcription factor CREB through its phosphorylation at Serine 133. Activation of CREB is involved in the regulation of various biological phenomena. To understand further the mechanisms of the regulation of CREB activity in response to activation of the cAMP and Ca2+ signaling pathways, we examined the roles of PLC gamma s in CREB activation in PC12 cells. siRNA-mediated reduction of the expression of PLC gamma 2, but not PLC gamma 1, inhibited both the phosphorylation of CREB at S133 and the activation of CREB-dependent transcription following treatment of cells with forskolin or ionomycin, which increases the intracellular concentrations of cAMP or Ca2+, respectively. Importantly, the siRNA targeting PLC gamma 2 completely abolished CREB activation by Ca2+ signaling but not by cAMP signaling. These results suggest that PLC gamma 2 functions as an essential signal transducer leading to CREB activation in response to activation of the Ca2+ signaling pathway and that the cAMP signaling pathway might activate CREB through phosphorylation of CREB by PKA and another signaling pathway mediated by PLC gamma 2.