Interaction of the CC-chemokine RANTES with glycosaminoglycans activates a p44/p42 mitogen-activated protein kinase-dependent signaling pathway and enhances human immunodeficiency virus type 1 infectivity
Interaction of the CC-chemokine RANTES with glycosaminoglycans activates a p44/p42 mitogen-activated protein kinase-dependent signaling pathway and enhances human immunodeficiency virus type 1 infectivity
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DOI：
10.1128/jvi.76.5.2245-2254.2002
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发表时间：
2002-03-01
影响因子：
5.4
通讯作者：
Trkola, A
中科院分区：
文献类型：
--
作者：
Chang, TLY;Gordon, CJ;Trkola, A
CC 趋化因子 RANTES 与其细胞表面受体的相互作用可转导多种细胞内信号：低浓度的 RANTES（1 至 10 nM）刺激 G 蛋白偶联受体 (GPCR) 活性，较高浓度 (1 muM) 则激活磷酸酪氨酸激酶 (PTK) 依赖性途径。在这里，我们表明较高的 RANTES 浓度会诱导多种蛋白质的快速酪氨酸磷酸化。几种 src 家族激酶（Fyn、Hck、Src）被激活，粘着斑激酶 p125 FAK 以及最终 p44/p42 丝裂原激活蛋白激酶 (MAPK) 家族的成员也被激活。该 PTK 信号通路可以独立于已知的 RANTES 七次跨膜 GPCR 被激活，因为它发生在缺乏任何此类 RANTES 受体的细胞中。相反，PTK 信号通路的激活依赖于细胞表面糖胺聚糖 (GAG) 的表达，因为在 GAG 缺陷的细胞中它不能被 RANTES 激活。我们之前已经证明 RANTES 可以增强和抑制人类免疫缺陷病毒 1 型 (HIV-1) 细胞的感染。在这里，我们表明，在缺乏 RANTES GPCR 但表达 GAG 的细胞中，PTK 和 MAPK 的激活与 RANTES 引起的 HIV-1 感染性增强有关。
The interaction of the CC-chemokine RANTES with its cell surface receptors transduces multiple intracellular signals: low concentrations of RANTES (1 to 10 nM) stimulate G-protein-coupled receptor (GPCR) activity, and higher concentrations (1 muM) activate a phosphotyrosine kinase (PTK)-dependent pathway. Here, we show that the higher RANTES concentrations induce rapid tyrosine phosphorylation of multiple proteins. Several src-family kinases (Fyn, Hck, Src) are activated, as is the focal adhesion kinase p125 FAK and, eventually, members of the p44/p42 mitogen-activated protein kinase (MAPK) family. This PTK signaling pathway can be activated independently of known seven-transmembrane GPCRs for RANTES because it occurs in cells that lack any such RANTES receptors. Instead, activation of the PTK signaling pathway is dependent on the expression of glycosaminoglycans (GAGs) on the cell surface, in that it could not be activated by RANTES in GAG-deficient cells. We have previously demonstrated that RANTES can both enhance and inhibit infection of cells with human immunodeficiency virus type 1 (HIV-1). Here we show that activation of both PTK and MAPK is involved in the enhancement of HIV-1 infectivity caused by RANTES in cells that lack GPCRs for RANTES but which express GAGs.