Abstract
Macrophage-derived chemokine (MDC/CC chemokine ligand 22 (CCL22)) mediates its cellular effects principally by binding to its receptor CCR4, and together they constitute a multifunctional chemokine/receptor system with homeostatic and inflammatory roles in the body. We report the CCL22-induced accumulation of phosphatidylinositol-(3,4,5)-trisphosphate (PI(3,4,5)P(3)) in the leukemic T cell line CEM. CCL22 also had the ability to chemoattract human Th2 cells and CEM cells in a pertussis toxin-sensitive manner. Although the PI(3,4,5)P(3) accumulation along with the pertussis toxin-susceptible phosphorylation of protein kinase B were sensitive to the two phosphoinositide 3-kinase inhibitors, LY294002 and wortmannin, cell migration was unaffected. However, cell migration was abrogated with the Rho-dependent kinase inhibitor, Y-27632. These data demonstrate that although there is PI(3,4,5)P(3) accumulation downstream of CCR4, phosphoinositide 3-kinase activity is a dispensable signal for CCR4-stimulated chemotaxis of Th2 cells and the CEM T cell line.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Cells, Cultured
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Chemokine CCL22
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Chemokines, CC / metabolism*
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Chemotaxis, Leukocyte* / drug effects
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Chemotaxis, Leukocyte* / immunology
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Enzyme Activation
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Humans
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Intracellular Signaling Peptides and Proteins
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Ligands
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Pertussis Toxin / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphatidylinositol Phosphates / metabolism
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Protein Serine-Threonine Kinases / metabolism
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Protein Serine-Threonine Kinases / physiology
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Receptors, CCR4
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Receptors, Chemokine / metabolism
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T-Lymphocytes / physiology*
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Th2 Cells / immunology
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rho-Associated Kinases
Substances
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CCL22 protein, human
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CCR4 protein, human
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Chemokine CCL22
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Chemokines, CC
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Intracellular Signaling Peptides and Proteins
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Ligands
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Phosphatidylinositol Phosphates
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Proto-Oncogene Proteins
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Receptors, CCR4
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Receptors, Chemokine
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phosphatidylinositol 3,4,5-triphosphate
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Pertussis Toxin
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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rho-Associated Kinases