Grass Carp Prolactin Gene: Structural Characterization and Signal Transduction for PACAP-induced Prolactin Promoter Activity.
Grass Carp Prolactin Gene: Structural Characterization and Signal Transduction for PACAP-induced Prolactin Promoter Activity.
复制标题
草鱼催乳素基因：PACAP 诱导的催乳素启动子活性的结构特征和信号转导
DOI：
10.1038/s41598-018-23092-0
复制
发表时间：
2018-03-15
影响因子：
4.6
通讯作者：
Wong AOL
中科院分区：
文献类型：
--
作者：
Lin C;Bai J;He M;Wong AOL
本研究对草鱼催乳素（PRL）基因进行了结构分析，并探讨了垂体腺苷酸环化酶激活肽（PACAP）调控PRL启动子活性的信号转导机制。在αT3-1细胞中，oPACAP 38可诱导PRL启动子活性，但能被PACAP拮抗剂阻断，VIP拮抗剂则不能。通过激活AC/cAMP和电压敏感性Ca 2+通道（VSCC）信号传导或诱导Ca 2+内流来模拟oPACAP 38的刺激作用。同时，PACAP诱导的PRL启动子活性被否定或抑制cAMP的产生，抑制PKA活性，去除细胞外Ca 2+，VSCC封锁，钙调蛋白（CaM）拮抗作用，和失活的CaM激酶II。通过用cAMP类似物替代oPACAP 38作为PRL启动子活性的刺激物，也观察到对L型VSCC、CaM和CaM激酶II抑制的类似敏感性。此外，PACAP诱导的PRL启动子活性也被PLC信号转导的抑制、IP 3受体介导的[Ca 2 +]i固定的减弱以及PI 3 K/P70 S6 K通路的阻断所阻断。PACAP诱导的PRL启动子激活可能涉及转录因子CREB的反式激活。这些结果表明，PACAP可以通过PAC 1介导的Ca 2 +/CaM/CaM激酶II级联与AC/cAMP/PKA通路的功能偶联来刺激PRL启动子活化。显然，其他信号通路，包括PLC/IP 3和PI 3 K/P70 S6 K级联，也可能参与PACAP诱导PRL基因转录。
In this study, structural analysis of grass carp prolactin (PRL) gene was performed and the signaling mechanisms for pituitary adenylate cyclase-activating peptide (PACAP) regulation of PRL promoter activity were investigated. In αT3-1 cells, PRL promoter activity could be induced by oPACAP38 which was blocked by PACAP antagonist but not the VIP antagonist. The stimulatory effect of oPACAP38 was mimicked by activation of AC/cAMP and voltage-sensitive Ca2+ channel (VSCC) signaling, or induction of Ca2+ entry. In parallel, PACAP-induced PRL promoter activity was negated or inhibited by suppressing cAMP production, inhibiting PKA activity, removal of extracellular Ca2+, VSCC blockade, calmodulin (CaM) antagonism, and inactivation of CaM kinase II. Similar sensitivity to L-type VSCC, CaM and CaM kinase II inhibition were also observed by substituting cAMP analog for oPACAP38 as the stimulant for PRL promoter activity. Moreover, PACAP-induced PRL promoter activity was also blocked by inhibition of PLC signaling, attenuation of [Ca2+]i immobilization via IP3 receptors, and blockade of PI3K/P70S6K pathway. The PACAP-induced PRL promoter activation may involve transactivation of the transcription factor CREB. These results suggest that PACAP can stimulate PRL promoter activation by PAC1 mediated functional coupling of the Ca2+/CaM/CaM kinase II cascades with the AC/cAMP/PKA pathway. Apparently, other signaling pathways, including PLC/IP3 and PI3K/P70S6K cascades, may also be involved in PACAP induction of PRL gene transcription.
登录
查看更多内容
影响因子：
--
作者：
BERWAER, M;MARTIAL, JA;DAVIS, JRE
通讯作者：
DAVIS, JRE
影响因子：
4.1
作者：
Lin, Chengyuan;Jiang, Xue;Wong, Anderson O. L.
通讯作者：
Wong, Anderson O. L.
影响因子：
--
作者：
Liu, JC;Baker, RE;Elsholtz, HP
通讯作者：
Elsholtz, HP
影响因子：
2.7
作者：
Astola, A;Ortiz, M;Valdivia, MM
通讯作者：
Valdivia, MM
影响因子：
2.9
作者：
BREDOW, S;KACSOH, B;KRUEGER, JM
通讯作者：
KRUEGER, JM