Human LZIP binds to CCR1 and differentially affects the chemotactic activities of CCR1-dependent chemokines
Human LZIP binds to CCR1 and differentially affects the chemotactic activities of CCR1-dependent chemokines
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DOI：
10.1096/fj.03-0867fje
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发表时间：
2004-03-01
期刊：
影响因子：
4.8
通讯作者：
Na, DS
中科院分区：
文献类型：
--
作者：
Ko, J;Jang, SW;Na, DS
与趋化因子受体结合的信号分子在趋化因子诱导的细胞迁移调节中起关键作用。为了表征CCR 1介导的细胞信号转导机制，我们使用酵母双杂交系统来鉴定CCR 1的细胞配体。已知LZIP是多种细胞类型中的转录因子，其被鉴定为CCR 1结合蛋白。虽然LZIP结合DNA的能力可能是使其作为转录因子发挥作用的原因，但其详细的功能和参与趋化性尚未确定。我们发现，LZIP结合到CCR 1的基础上的哺乳动物双杂交试验和免疫沉淀实验的结果。LZIP的21-260个残基是与CCR 1相互作用所必需的。使用LZIP转染细胞的趋化性测定结果显示，LZIP增强Lkn-1诱导的趋化性，而由与CCR 1结合的其他CC趋化因子（包括MIP-1 α、RANTES或HCC-4）诱导的趋化活性不受LZIP过表达的影响。这些数据表明，LZIP结合CCR 1和CCR 1和LZIP之间的相互作用参与调节Lkn-1依赖的细胞迁移，而不影响其他CC趋化因子结合CCR 1的趋化活性。
Signaling molecules that bind to chemokine receptors should play key roles in regulation of cell migration induced by chemokines. To characterize the CCR1-mediated cellular signal transduction mechanism, we used the yeast two-hybrid system to identify a cellular ligand for CCR1. LZIP, which has been known as a transcription factor in various cell types, was identified as a CCR1 binding protein. Although the ability of LZIP to bind DNA is possibly what allows it to function as a transcription factor, its detailed function and participation in chemotaxis have not been established. We found that LZIP binds to CCR1 based on results of a mammalian two-hybrid assay and immunoprecipitation experiments. The 21-260 residues of LZIP were essential for interaction with CCR1. Results from a chemotaxis assay using LZIP transfected cells showed that LZIP enhanced Lkn-1-induced chemotaxis, whereas the chemotactic activities induced by other CC chemokines that bind to CCR1, including MIP-lalpha, RANTES, or HCC-4, were not affected by LZIP overexpression. These data indicate that LZIP binds to CCR1 and that the interaction between CCR1 and LZIP participates in regulation of Lkn-1-dependent cell migration without affecting the chemotactic activities of other CC chemokines that bind to CCR1.