In previous study, we found that the chemokine receptor 9 （CCR9） was highly expressed on CD4^＋T cells from patients with T-cell lineage acute lymphocytic leukemia （T-ALL） and mediated leukemia cell infiltration a...In previous study, we found that the chemokine receptor 9 （CCR9） was highly expressed on CD4^＋T cells from patients with T-cell lineage acute lymphocytic leukemia （T-ALL） and mediated leukemia cell infiltration and metastasis. Combined use of interleukin 2 （IL-2） and IL-4 promoted the internalization of CCR9 and therefore attenuated leukemia cell infiltration and metastasis. In this study, we preliminarily investigated the mechanism of internalization of CCR9 on MOLT4 cell model （a human leukemia T-cell line, naturally expresses CCR9） and found that IL-2 upregulated the cell surface expression of IL-4Rα （CD124） greatly, whereas IL-4 had no significant influence on α （CD25） and β subunits （CD122） of IL-2R. Moreover, specific inhibitors, such as staurosporine, H89 and heparin, inhibited internalization of CCR9, which indicated a role of protein kinase C （PKC） and G protein-coupled kinase 2 （GRK2）, respectively. Furthermore, GRK2 was upregulated and translocated to cell membrane in IL-2 and IL-4 treated cells which indicated that PKC could be a prerequisite for GRK2 activity.展开更多
基金This study was supported by the National Natural Science Foundation of China （No. 30570780）, National Ministry of Education Doctoral Fund （No. 200804860039） and Department of Science and Technology of Hubei Province, China （No. 2006AA301B64）.
文摘In previous study, we found that the chemokine receptor 9 （CCR9） was highly expressed on CD4^＋T cells from patients with T-cell lineage acute lymphocytic leukemia （T-ALL） and mediated leukemia cell infiltration and metastasis. Combined use of interleukin 2 （IL-2） and IL-4 promoted the internalization of CCR9 and therefore attenuated leukemia cell infiltration and metastasis. In this study, we preliminarily investigated the mechanism of internalization of CCR9 on MOLT4 cell model （a human leukemia T-cell line, naturally expresses CCR9） and found that IL-2 upregulated the cell surface expression of IL-4Rα （CD124） greatly, whereas IL-4 had no significant influence on α （CD25） and β subunits （CD122） of IL-2R. Moreover, specific inhibitors, such as staurosporine, H89 and heparin, inhibited internalization of CCR9, which indicated a role of protein kinase C （PKC） and G protein-coupled kinase 2 （GRK2）, respectively. Furthermore, GRK2 was upregulated and translocated to cell membrane in IL-2 and IL-4 treated cells which indicated that PKC could be a prerequisite for GRK2 activity.
