Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Cell Immunol. 2012;272(2):230-41. doi: 10.1016/j.cellimm.2011.09.015. Epub 2011 Oct 20.
Chemokine receptors CXCR7 and CXCR4 bind to the same ligand stromal cell derived factor-1alpha (SDF-1α/CXCL12). We assessed the downstream signaling pathways mediated by CXCL12-CXCR7 interaction in Jurkat T cells. All experiments were carried out after functionally blocking the CXCR4 receptor. CXCL12, on binding CXCR7, induced phosphorylation of extra cellular regulated protein kinases (ERK 1/2) and Akt. Selective inhibition of each signal demonstrated that phosphorylated ERK 1/2 is essential for chemotaxis and survival of T cells whereas activation of Akt promotes only cell survival. Another interesting finding of this study is that CXCL12-CXCR7 interaction under normal physiological conditions does not activate the p38 pathway. Furthermore, we observed that the CXCL12 signaling via CXCR7 is Giα independent. Our findings suggest that CXCR7 promotes cell survival and does not induce cell death in T cells. The CXCL12 signaling via CXCR7 may be crucial in determining the fate of the activated T cells.
趋化因子受体 CXCR7 与 CXCR4 结合相同的配体基质细胞衍生因子-1α (SDF-1α/CXCL12)。我们评估了 Jurkat T 细胞中 CXCL12-CXCR7 相互作用介导的下游信号通路。所有实验均在功能阻断 CXCR4 受体后进行。CXCL12 与 CXCR7 结合后，诱导细胞外调节蛋白激酶 (ERK1/2) 和 Akt 的磷酸化。每种信号的选择性抑制表明，磷酸化的 ERK1/2 对于 T 细胞的趋化性和存活是必需的，而 Akt 的激活仅促进细胞存活。本研究的另一个有趣发现是，正常生理条件下 CXCL12-CXCR7 相互作用不会激活 p38 途径。此外，我们观察到 CXCR7 介导的 CXCL12 信号传导不依赖于 Giα。我们的研究结果表明，CXCR7 促进 T 细胞的存活，而不会诱导细胞死亡。通过 CXCR7 的 CXCL12 信号可能对决定激活的 T 细胞的命运至关重要。
