Regulation of chemotactic and proadhesive responses to chemoattractant receptors by RGS (Regulator of G-protein Signaling) family members

Regulation of chemotactic and proadhesive responses to chemoattractant receptors by RGS (Regulator of G-protein Signaling) family members
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DOI:
10.1074/jbc.273.43.28040
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发表时间:
1998-10-23
影响因子:
4.8
通讯作者:
Butcher, EC
Butcher, EC
中科院分区:
生物学2区
文献类型:
--
作者:
Bowman, EP;Campbell, JJ;Butcher, EC

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蛇形 G α(i) 连接受体支持白细胞和其他细胞类型的快速粘附和定向迁移。介导和调节趋化剂导向的粘附和运动的细胞内机制现在才开始被探索。 RGS(G 蛋白信号调节蛋白)是最近描述的一个家族,它通过充当 GTP 酶激活蛋白来调节 G α(i) 刺激的途径。对于参与粘附和趋化性的 G α(i) 蛋白的 GTP 酶活性,或者它们对这些反应的调节的重要性,人们知之甚少。使用瞬时转染的淋巴细胞作为模型系统,我们发现 RGS1、RGS3 和 RGS4 的表达抑制趋化剂诱导的迁移。相比之下,G α(q) 活性的调节剂 RGS2 对细胞向任何化学引诱剂的迁移没有影响。 RGS1、RGS3 和 RGS4 也减少了快速趋化剂触发的粘附,尽管从数量上看,促粘附反应对 RGS 作用的敏感性似乎不如趋化性。结果表明,G α(i) 信号的持续时间可能是白细胞趋化反应中特别重要的参数,并证明了 RGS 家族成员调节细胞粘附和迁移的潜力。 行为。
Serpentine G alpha(i)-linked receptors support rapid adhesion and directed migration of leukocytes and other cell types. The intracellular mechanisms mediating and regulating chemoattractant-directed adhesion and locomotion are only now beginning to be explored. RGS (for regulator of G-protein signaling) proteins are a recently described family that regulate G alpha(i)-stimulated pathways by acting as GTPase-activating proteins. Little is known about the GTPase activity of the G alpha(i) proteins involved in adhesion and chemotaxis, or the significance of their regulation to these responses. Using transiently transfected lymphoid cells as a model system, we show that expression of RGS1, RGS3, and RGS4 inhibits chemoattractant-induced migration. In contrast, RGS2, a regulator of G alpha(q) activity, had no effect on cell migration to any chemoattractant. RGS1, RGS3, and RGS4 also reduced rapid chemoattractant-triggered adhesion, although the proadhesive response appears quantitatively less sensitive to RGS action than chemotaxis, The results suggest that the duration of the G alpha(i) signal may be a particularly important parameter in the chemotactic responses of leukocytes, and demonstrate the potential for RGS family members to regulate cellular adhesive and migratory behaviors.