Abstract
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-4Ralpha (CD124) greatly, whereas IL-4 had no significant influence on alpha (CD25) and beta 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Line, Tumor
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Endocytosis / drug effects*
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Flow Cytometry
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G-Protein-Coupled Receptor Kinase 2 / genetics
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G-Protein-Coupled Receptor Kinase 2 / metabolism
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G-Protein-Coupled Receptor Kinase 3 / genetics
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G-Protein-Coupled Receptor Kinase 3 / metabolism
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G-Protein-Coupled Receptor Kinase 5 / genetics
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G-Protein-Coupled Receptor Kinase 5 / metabolism
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G-Protein-Coupled Receptor Kinases / genetics
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G-Protein-Coupled Receptor Kinases / metabolism
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Gene Expression Regulation, Leukemic / drug effects
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Humans
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Interleukin-2 / pharmacology*
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Interleukin-2 Receptor alpha Subunit / metabolism
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Interleukin-2 Receptor beta Subunit / metabolism
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Interleukin-4 / pharmacology*
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Isoquinolines / pharmacology
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Leukemia, T-Cell / genetics
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Leukemia, T-Cell / metabolism
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Leukemia, T-Cell / pathology
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Protein Kinase Inhibitors / pharmacology
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RNA Interference
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Receptors, CCR / metabolism*
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Receptors, Interleukin-2 / metabolism
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Receptors, Interleukin-4 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sulfonamides / pharmacology
Substances
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CC chemokine receptor 9
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Interleukin-2
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Interleukin-2 Receptor alpha Subunit
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Interleukin-2 Receptor beta Subunit
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Isoquinolines
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Protein Kinase Inhibitors
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Receptors, CCR
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Receptors, Interleukin-2
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Receptors, Interleukin-4
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Sulfonamides
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Interleukin-4
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Cyclic AMP-Dependent Protein Kinases
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G-Protein-Coupled Receptor Kinase 3
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GRK2 protein, human
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GRK3 protein, human
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G-Protein-Coupled Receptor Kinase 2
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G-Protein-Coupled Receptor Kinase 5
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G-Protein-Coupled Receptor Kinases
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G-protein-coupled receptor kinase 6
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GRK5 protein, human
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide