The role of G-protein in matrix-mediated motility of highly and poorly invasive melanoma cells.
The role of G-protein in matrix-mediated motility of highly and poorly invasive melanoma cells.
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G 蛋白在高侵袭性和低侵袭性黑色素瘤细胞基质介导的运动中的作用。
DOI：
10.1002/ijc.2910480121
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发表时间：
1991
影响因子：
6.4
通讯作者：
Furcht,LT
中科院分区：
文献类型：
--
作者：
Lester,BR;Weinstein,LS;McCarthy,JB;Sun,ZQ;Smith,RS;Furcht,LT
与弱侵袭性细胞对应物相比，来自 2 个具有高侵袭能力的 K1735 鼠黑色素瘤克隆的膜显示出百日咳毒素 (PT) 底物量增加。使用一组特异性 G 蛋白抗体，我们鉴定出 Giα2 是高度侵袭性细胞中独特丰富的 PT 敏感 G 蛋白。此外，RNA 杂交结果证实了免疫印迹观察结果，即 Giα2 在强侵袭性细胞中存在较高水平。这一结果表明，高侵袭性细胞中 Giα2 表达的升高并不完全是由于翻译效率或蛋白质降解的差异，而是与 RNA 转录起始、加工和/或降解的改变有关。 PT 对 G1α 亚基的 ADP 核糖基化抑制了 2 个高侵袭性克隆的纤连蛋白、层粘连蛋白和 IV 型胶原蛋白刺激的运动性，而对侵袭性低的克隆的细胞进行 PT 处理导致纤连蛋白、层粘连蛋白或 IV 型胶原蛋白刺激的较低运动性很少或没有减少。此外，高或低侵袭性 KI735 克隆的 PT 处理不会导致细胞 cAMP 积累的任何改变，表明 PT 底物不与腺苷酸环化酶复合物连接。数据表明，一种 PT 敏感的 G 蛋白（可能是 Giα2）调节第二信使通路，有助于提高高度侵袭性 KI735 细胞的运动性。
Membranes from 2 K1735 murine melanoma clones of high invasive capacity show increased amounts of pertussis toxin (PT) substrate when compared to a weakly invasive cellular counterpart. Using a panel of specific G‐protein antibodies, we identified Giα2as the PT‐sensitive G‐protein uniquely abundant in highly invasive cells. In addition, RNA hybridization results confirm the immunoblot observations that Giα2is present at higher levels in strongly invasive cells. This result suggests that the elevated expression of Giα2in highly invasive cells is not entirely due to differences in either translational efficiency or protein degradation but is related to altered RNA transcriptional initiation, processing and/or degradation. ADP‐ribosylation of G1α‐subunits by PT inhibited the fi‐bronectin, laminin and collagen type‐IV‐stimulated motility of the 2 highly invasive clones, while PT treatment of cells from a poorly invasive clone resulted in little or no reduction of the fibronectin, laminin or collagen type‐IV‐stimulated lower motility. Furthermore, PT treatment of highly or poorly invasive KI735 clones does not result in any alteration in cellular cAMP accumulation, suggesting that the PT substrate is not linked with the adenylyl cyclase enzyme complex. The data suggest that a PT‐sensitive G‐protein, probably Giα2, regulates second messenger pathways that contribute to elevated motility in highly invasive KI735 cells.