Otte Maik, Kliewer Andrea, Schütz Dagmar, Reimann Christiane, Schulz Stefan, Stumm Ralf
Institute of Pharmacology and Toxicology, University Hospital, Friedrich-Schiller University Jena, Germany.
Institute of Pharmacology and Toxicology, University Hospital, Friedrich-Schiller University Jena, Germany.
FEBS Lett. 2014 Dec 20;588(24):4769-75. doi: 10.1016/j.febslet.2014.11.009. Epub 2014 Nov 18.
C-X-C motif chemokine 12/C-X-C chemokine receptor type 4 (CXCL12/CXCR4) signaling is involved in ontogenesis, hematopoiesis, immune function and cancer. Recently, the orphan chemokine CXCL14 was reported to inhibit CXCL12-induced chemotaxis - probably by allosteric modulation of CXCR4. We thus examined the effects of CXCL14 on CXCR4 regulation and function using CXCR4-transfected human embryonic kidney (HEK293) cells and Jurkat T cells. CXCL14 did not affect dose-response profiles of CXCL12-induced CXCR4 phosphorylation, G protein-mediated calcium mobilization, dynamic mass redistribution, kinetics of extracellular signal-regulated kinase 1 (ERK1) and ERK2 phosphorylation or CXCR4 internalization. Hence, essential CXCL12-operated functions of CXCR4 are insensitive to CXCL14, suggesting that interactions of CXCL12 and CXCL14 pathways depend on a yet to be identified CXCL14 receptor.
C-X-C基序趋化因子12/C-X-C趋化因子受体4（CXCL12/CXCR4）信号传导参与个体发育、造血、免疫功能及癌症过程。最近，据报道孤儿趋化因子CXCL14可抑制CXCL12诱导的趋化作用——可能是通过对CXCR4的变构调节。因此，我们使用转染了CXCR4的人胚肾（HEK293）细胞和Jurkat T细胞研究了CXCL14对CXCR4调节及功能的影响。CXCL14不影响CXCL12诱导的CXCR4磷酸化、G蛋白介导的钙动员、动态质量再分布、细胞外信号调节激酶1（ERK1）和ERK2磷酸化动力学或CXCR4内化的剂量反应曲线。因此，CXCR4的基本CXCL12操纵功能对CXCL14不敏感，这表明CXCL12和CXCL14途径的相互作用取决于尚未确定的CXCL14受体。
