The CXCR1 tail mediates beta1 integrin-dependent cell migration via MAP kinase signaling.

The CXCR1 tail mediates beta1 integrin-dependent cell migration via MAP kinase signaling.
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CXCR1 尾部通过 MAP 激酶信号传导介导 β1 整合素依赖性细胞迁移。

DOI:
10.1016/j.bbrc.2005.04.139
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发表时间:
2005
影响因子:
3.1
通讯作者:
Rose,DavidM
Rose,DavidM
中科院分区:
生物学4区
文献类型:
--
作者:
Liu-Bryan,Ru;Pay,Salih;Schraufstatter,IngridU;Rose,DavidM

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在这项研究中,我们研究了IL-8如何诱导白细胞迁移的主要β1整合素配体来源于细胞外基质蛋白纤连蛋白。我们通过将CXCR 1和CXCR 2转染到大鼠嗜碱性白血病(RBL)细胞和人单核细胞THP-1细胞中,评估了IL-8受体信号传导的个体贡献。表达CXCR 1的细胞响应于IL-8而在α4β1和α5β1整联蛋白的纤连蛋白配体上迁移,而表达CXCR 2的细胞则不迁移。表达含有CXCR 2胞质尾的嵌合CXCR 1受体的RBL细胞的迁移大大减弱,而表达具有CXCR 1尾的CXCR 2嵌合体的细胞的迁移增强。最后,p38和JNK MAP激酶抑制剂阻断IL-8诱导的CXCR 1(+)细胞迁移。我们的结论是,IL-8刺激β1整合素介导的白细胞通过CXCR 1在纤连蛋白上的迁移依赖于CXCR 1的C端胞质结构域和随后的p38和JNK MAPK信号传导。
In this study, we examined how IL-8 induces leukocyte migration on major β1 integrin ligands derived from the extracellular matrix protein fibronectin. We assessed individual contributions of signaling by IL-8 receptors by transfection of CXCR1 and CXCR2 into rat basophilic leukemia (RBL) cells and human monocytic THP-1 cells. CXCR1 expressing cells migrated on the fibronectin ligands for α4β1 and α5β1 integrins in response to IL-8, whereas CXCR2 expressing cells did not. RBL cells expressing the chimeric CXCR1 receptor containing the cytoplasmic tail of CXCR2 had greatly blunted migration, while cells expressing the CXCR2 chimera with the tail of CXCR1 had augmented migration. Last, inhibitors of p38 and JNK MAP kinases blocked IL-8-induced migration in CXCR1(+) cells. We conclude that IL-8 stimulated β1 integrin-mediated leukocyte migration on fibronectin through CXCR1 is dependent on the C-terminal cytoplasmic domain of CXCR1 and subsequent p38 and JNK MAPK signaling.