Angiotensin II activates mitogen-activated protein kinase via protein kinase C and Ras/Raf-1 kinase in bovine adrenal glomerulosa cells.

Angiotensin II activates mitogen-activated protein kinase via protein kinase C and Ras/Raf-1 kinase in bovine adrenal glomerulosa cells.
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血管紧张素 II 在牛肾上腺肾小球细胞中通过蛋白激酶 C 和 Ras/Raf-1 激酶激活丝裂原激活蛋白激酶。

DOI:
10.1210/endo.139.4.5865
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发表时间:
1998
期刊:
影响因子:
4.8
通讯作者:
K. Catt
K. Catt
中科院分区:
医学2区
文献类型:
--
作者:
Y. Tian;R. Smith;T. Balla;K. Catt

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血管紧张素II(Ang II)刺激牛肾上腺肾小球细胞的生长和有丝分裂,但很少有人知道介导这些反应的信号通路。对培养的牛肾上腺肾小球细胞中的生长促进途径的分析显示,Ang II通过AT 1受体起作用,引起丝裂原活化蛋白激酶(MAPK)的快速但短暂的激活,ED 50为10-50 pM。虽然无论是Ca 2+内流或Ca 2+释放从细胞内的商店是不够的激活MAPK,Ca 2+似乎在这种反应中发挥了许可的作用。血管紧张素II诱导的MAPK激活的一个主要组成部分是不敏感的百日咳毒素(PTX),虽然一个较小的PTX敏感的组件不能被排除在外。Ang Ⅱ还诱导ras和raf-1激酶的快速激活,其时间过程与MAPK的时间过程相关。蛋白激酶C(PKC)的激活佛波醇12-肉豆蔻酸酯13-乙酸酯是足够的激活MAPK和raf-1激酶。然而,尽管PKC耗竭对Ang II诱导的raf-1激酶激活没有影响,但它减弱了Ang II诱导的MAPK激活。血管紧张素II还刺激了迁移率的raf-1,反映了过度磷酸化的激酶。然而,与其激活不同,raf-1过度磷酸化依赖于PKC,其时间过程与激活无关,而是与激酶的失活有关。总之,这些研究结果表明,血管紧张素II刺激多种途径,MAPK激活通过PKC和ras/raf-1激酶在牛肾上腺肾小球细胞。
Angiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal glomerulosa cells, but little is known about the signaling pathways that mediate these responses. An analysis of the growth-promoting pathways in cultured bovine adrenal glomerulosa cells revealed that Ang II, acting via the AT1 receptor, caused rapid but transient activation of mitogen-activated protein kinase (MAPK), with an ED50 of 10-50 pM. Although neither Ca2+ influx nor Ca2+ release from intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a permissive role in this response. A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded. Ang II also induced the rapid activation of ras and raf-1 kinase with time-courses that correlated with that of MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was sufficient to activate both MAPK and raf-1 kinase. However, whereas PKC depletion had no effect on Ang II-induced raf-1 kinase activation, it attenuated Ang II-induced MAPK activation. Ang II also stimulated a mobility shift of raf-1, reflecting hyperphosphorylation of the kinase. However, unlike its activation, raf-1 hyperphosphorylation was dependent on PKC and its time-course correlated not with activation, but rather with deactivation of the kinase. Taken together, these findings indicate that Ang II stimulates multiple pathways to MAPK activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells.
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