Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes.
Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes.
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DOI：
10.1084/jem.20071267
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发表时间：
2007-10-29
期刊：
影响因子：
--
通讯作者：
Lund FE
中科院分区：
文献类型：
--
作者：
Shi G;Partida-Sánchez S;Misra RS;Tighe M;Borchers MT;Lee JJ;Simon MI;Lund FE
CD 38控制白细胞对某些但不是全部趋化因子的趋化性，表明白细胞中的趋化因子受体信号传导比以前认识到的更加多样化。为了确定这种信号异质性的基础，我们研究了以CD 38依赖性方式发出信号的趋化因子受体，并确定了一种新的“替代”趋化因子受体信号通路。类似于“经典”信号传导途径，旁路趋化因子受体途径被含有Gαi2的Gi蛋白激活。然而，与经典途径不同，旁路途径也依赖于G蛋白的Gq类。我们表明，Gα q缺陷型中性粒细胞和树突状细胞（DC）在用N-甲酰基甲硫氨酰亮氨酰苯丙氨酸和CC趋化因子配体（CCL）3（中性粒细胞）刺激后，或在用CCL 2、CCL 19、CCL 21和CXC趋化因子配体（CXCL）12（DC）刺激后，会产生缺陷性钙和趋化反应。相比之下，Gα q缺陷型T细胞对CXCL 12和CCL 19的应答保持完整。因此，替代性趋化因子受体途径仅控制一部分细胞的迁移。无论如何，新的替代趋化因子受体信号传导途径似乎对炎症反应的启动至关重要，因为Gαq是异硫氰酸荧光素致敏后DC从皮肤迁移到引流淋巴结以及接触致敏后单核细胞从骨髓迁移到发炎皮肤所必需的。
CD38 controls the chemotaxis of leukocytes to some, but not all, chemokines, suggesting that chemokine receptor signaling in leukocytes is more diverse than previously appreciated. To determine the basis for this signaling heterogeneity, we examined the chemokine receptors that signal in a CD38-dependent manner and identified a novel “alternative” chemokine receptor signaling pathway. Similar to the “classical” signaling pathway, the alternative chemokine receptor pathway is activated by Gαi2-containing Gi proteins. However, unlike the classical pathway, the alternative pathway is also dependent on the Gq class of G proteins. We show that Gαq-deficient neutrophils and dendritic cells (DCs) make defective calcium and chemotactic responses upon stimulation with N-formyl methionyl leucyl phenylalanine and CC chemokine ligand (CCL) 3 (neutrophils), or upon stimulation with CCL2, CCL19, CCL21, and CXC chemokine ligand (CXCL) 12 (DCs). In contrast, Gαq-deficient T cell responses to CXCL12 and CCL19 remain intact. Thus, the alternative chemokine receptor pathway controls the migration of only a subset of cells. Regardless, the novel alternative chemokine receptor signaling pathway appears to be critically important for the initiation of inflammatory responses, as Gαq is required for the migration of DCs from the skin to draining lymph nodes after fluorescein isothiocyanate sensitization and the emigration of monocytes from the bone marrow into inflamed skin after contact sensitization.