RGS14, a GTPase-activating protein for Giα, attenuates Giα- and G13α-mediated signaling pathways
RGS14, a GTPase-activating protein for Giα, attenuates Giα- and G13α-mediated signaling pathways
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DOI：
10.1124/mol.58.3.569
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发表时间：
2000-09-01
影响因子：
3.6
通讯作者：
Kehrl, JH
中科院分区：
文献类型：
--
作者：
Cho, H;Kozasa, T;Kehrl, JH
G 蛋白信号传导调节蛋白 (RGS) 是一个由大约 20 种蛋白组成的家族，可通过异三聚体 G 蛋白偶联受体负向调节信号传导。 RGS 蛋白充当某些 Ga 亚基的 GTP 酶激活蛋白 (GAP) 和 Gq α 的效应拮抗剂。小鼠 RGS14 编码具有 N 端 RGS 结构域的 547 个氨基酸蛋白，该蛋白在淋巴组织中高表达。在这项研究中，我们证明 RGS14 是 Gi α 亚家族成员的 GAP，它可以减弱白细胞介素 8 受体介导的丝裂原激活蛋白激酶的激活。然而，RGS14 不表现出针对 Gs α 或 Gq α 的 GAP 活性，也不调节 Gs α 或 Gq α 介导的信号传导途径。尽管 RGS14 不充当 G12/13 α 的 GAP，但它会损害由 G13 α 的组成型活性突变体 (G13 α Q226L) 或毒蕈碱 1 型受体的卡巴胆碱刺激诱导的 c-fos 血清反应元件激活。 RGS14 突变体 (EN92/93AA) 不会阻断 Gi α 相关信号传导，也会抑制血清反应元件激活。 RGS14 主要定位于细胞质中，但可以通过 G13 α Q226L 的表达将其招募到细胞膜上。尽管 RGS14 在淋巴细胞中组成型表达，但激活 B 或 T 淋巴细胞的药物会进一步增强其水平。综上所述，我们的结果表明，淋巴细胞激活后产生的信号可能通过 RGS14 直接影响淋巴细胞中 Gi α 或 G13 α 介导的细胞过程，例如粘附和迁移。
Regulator of G protein signaling (RGS) proteins are a family of approximately 20 proteins that negatively regulate signaling through heterotrimeric G protein-coupled receptors. The RGS proteins act as GTPase-activating proteins (GAPs) for certain Ga subunits and as effector antagonists for Gq alpha. Mouse RGS14 encodes a 547-amino-acid protein with an N-terminal RGS domain, which is highly expressed in lymphoid tissues. In this study, we demonstrate that RGS14 is a GAP for Gi alpha subfamily members and it attenuates interleukin-8 receptor-mediated mitogen-activated protein kinase activation. However, RGS14 does not exhibit GAP activity toward Gs alpha or Gq alpha nor does it regulate Gs alpha- or Gq alpha-mediated signaling pathways. Although RGS14 does not act as a GAP for G12/13 alpha, it impairs c-fos serum response element activation induced by either a constitutively active mutant of G13 alpha (G13 alpha Q226L) or by carbachol stimulation of muscarinic type 1 receptors. An RGS14 mutant (EN92/93AA), which does not block Gi alpha-linked signaling, also inhibits serum response element activation. RGS14 localizes predominantly in the cytosol, but it can be recruited to membranes by expression of G13 alpha Q226L. Although RGS14 is constitutively expressed in lymphoid cells, agents that activate B or T lymphocytes further enhance its levels. Taken together, our results suggest that signals generated after lymphocyte activation may via RGS14 directly impinge on Gi alpha- or G13 alpha-mediated cellular processes in lymphocytes, such as adhesion and migration.