D2s dopamine receptor mediates phospholipase D and antiproliferation.
D2s dopamine receptor mediates phospholipase D and antiproliferation.
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D2s 多巴胺受体介导磷脂酶 D 和抗增殖作用。
DOI：
10.1016/j.mce.2003.07.001
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发表时间：
2003
影响因子：
4.1
通讯作者：
Senogles,SusanE
中科院分区：
文献类型：
--
作者：
Senogles,SusanE
D2多巴胺受体，短型（D2 s）已经显示在用D2 s受体稳定转染的GH4衍生细胞中刺激磷脂酶D（PLD）活性，而不依赖于磷脂酶C（PLC）活性的激活[Mol. 58（2000）455]。D2 s的激动剂活化已显示介导相同细胞系中生长的抑制[J. Biol. Chem. 276（1992）24169; Endocrinology 134（1994）783]。在本研究中，使用基于EB病毒（EBV）的载体产生D2 s-HEK 293细胞。D2 s对PLD的刺激可通过Rho A的转染而增强，但不能通过Cdc 42或Rac的转染而被N19 Rho A（Rho A的显性负性形式）的转染所抵消。添加0.5%乙醇降低多巴胺激动剂抑制D2 s-HEK 293细胞生长的能力，表明PLD参与D2 s信号传导的抗增殖作用。此外，N19 Rho A的表达消除了D2 s抑制[3 H]胸苷掺入的能力，而N19 Cdc 42或N17 Rac的表达没有影响。这些结果表明PLD的D2 s刺激是Rho A依赖的，并且沿着导致D2 s受体激活的抗增殖效应的信号通路。
The D2 dopamine receptor, short form (D2s) has been shown to stimulate phospholipase D (PLD) activity independent of activation of phospholipase C (PLC) activity in GH4 derived cells stably transfected with the D2s receptor [Mol. Pharm. 58 (2000) 455]. Agonist activation of D2s has been shown to mediate the inhibition of growth in the same cell line [J. Biol. Chem. 276 (1992) 24169; Endocrinology 134 (1994) 783]. In the present study, D2s-HEK 293 cells were generated using Epstein-Barr virus (EBV) based vectors. The stimulation of PLD by D2s can be augmented by the transfection of Rho A, but not Cdc 42 or Rac and nullified by transfection of N19 Rho A, a dominant negative form of Rho A. Addition of ethanol, at 0.5% reduced the ability of dopamine agonists to inhibit growth in D2s-HEK 293 cells, suggesting that PLD is involved in the antiproliferative effects of D2s signaling. In addition, the expression of N19 Rho A ablated the ability of the D2s to inhibit [3H ] thymidine incorporation, while the expression of N19 Cdc 42 or N17 Rac had no effect. These results suggest that the D2s stimulation of PLD is Rho A dependent and lies along the signaling pathway which leads to the antiproliferative effects of D2s receptor activation.