G protein-mediated mitogen-activated protein kinase activation by two dopamine D2 receptors
G protein-mediated mitogen-activated protein kinase activation by two dopamine D2 receptors
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DOI：
10.1006/bbrc.1999.0286
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发表时间：
1999-03-05
影响因子：
3.1
通讯作者：
Baik, JH
中科院分区：
文献类型：
--
作者：
Choi, EY;Jeong, DW;Baik, JH
多巴胺 D2 受体的两种亚型 D2L（长）和 D2S（短）的不同之处在于，在假定的受体第三个细胞内环内插入了 D2L 特异的 29 个氨基酸，这对于 G 蛋白偶联的选择性似乎很重要。我们已经生成了表达 D2L 和 D2S 的中国仓鼠卵巢 (CHO) 细胞，并在这些细胞中检查了丝裂原激活蛋白激酶 (MAPK) 途径的调节。 D2L 和 D2S 均介导 MAPK 的快速瞬时激活，其中 p42-kDa MAPK 的显性激活。百日咳毒素治疗完全消除了 D2L 和 D2S 介导的 MAPK 刺激，表明这两种受体在该信号传导中与百日咳毒素敏感的 G 蛋白偶联。 D2L 和 D2S 受体介导的 MAPK 刺激因 β-肾上腺素受体激酶 (β ARKct) C 端的共表达而显着减弱，β-肾上腺素受体激酶 (β ARKct) 选择性抑制 G β γ 介导的信号转导。对 D2L 和 D2S 介导的 MAPK 激活的进一步分析表明，D2L 介导的 MAPK 激活不受 PKC 耗竭的显着影响，也不受金雀异黄素的部分影响。相反，D2S 介导的 MAPK 激活可能会受到 PHC 消耗的抑制，而金雀异黄素能够完全抑制 D2S 介导的 MAPK 激活。总之，这些结果表明 D2L 和 D2S 介导的 MAPK 激活主要是 G beta gamma 亚基介导的信号传导，并且蛋白激酶 C 和酪氨酸磷酸化参与这些信号传导途径。 (C) 1999 年学术出版社。
Two isoforms of dopamine D2 receptor, D2L (long) and D2S (short), differ by the insertion of 29 amino acids specific to D2L within the putative third intracellular loop of the receptor, which appears to be important in selectivity for G-protein coupling. We have generated D2L- and D2S-expressing Chinese hamster ovary (CHO) cells, and regulation of the mitogen-activated protein kinase (MAPK) pathway was examined in these cells. Both D2L and D2S mediated a rapid and transient activation of MAPK with dominant activation of p42-kDa MAPK. Pertussis toxin treatment completely abrogated stimulation of MAPK mediated by D2L and D2S, demonstrating that both receptors couple to pertussis toxin-sensitive G proteins in this signaling. Stimulation of MAPK mediated by both D2L and D2S receptor was markedly attenuated by coexpression of the C-terminus of beta-adrenergic receptor kinase (beta ARKct), which selectively inhibits G beta gamma-mediated signal transduction. Further analysis of D2L- and D2S-mediated MAPK activation demonstrated that D2L-mediated MAPK activation was not significantly affected by PKC depletion or partially affected by genistein. In contrast, D2S-mediated MAPK activation was potentially inhibited by PHC depletion and genistein was capable of completely inhibiting D2S-mediated MAPK activation. Together, these results suggest that D2L- and D2S-mediated MAPK activation is predominantly G beta gamma subunit-mediated signaling and that protein kinase C and tyrosine phosphorylations are involved in these signaling pathways. (C) 1999 Academic Press.