Abstract
Cell migration is a complex phenomenon that is stimulated by chemoattractive factors such as chemokines, a family of ligands for G protein-coupled receptors (GPCRs). In contrast, factors that suppress cell migration, and the mechanism of their action, remain largely unknown. In this study, we show that endothelin, a GPCR ligand, inhibits cell motility in a manner dependent upon signaling through the c-Jun N-terminal kinase (JNK) pathway. We further demonstrate that this effect is dependent upon Src kinase and small GTPases Rac1 and Cdc42. These findings provide new insight into GPCR-mediated regulation of cell migration.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Movement / drug effects
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Cells, Cultured
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Endothelins / metabolism*
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Endothelins / pharmacology
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Humans
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4*
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Mitogen-Activated Protein Kinase Kinases / drug effects
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Mitogen-Activated Protein Kinase Kinases / genetics
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / drug effects
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Mitogen-Activated Protein Kinases / metabolism*
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Signal Transduction
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cdc42 GTP-Binding Protein / drug effects
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cdc42 GTP-Binding Protein / metabolism*
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rac1 GTP-Binding Protein / drug effects
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rac1 GTP-Binding Protein / metabolism*
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src-Family Kinases / drug effects
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src-Family Kinases / metabolism*
Substances
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Endothelins
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src-Family Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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MAP2K4 protein, human
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Mitogen-Activated Protein Kinase Kinases
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cdc42 GTP-Binding Protein
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rac1 GTP-Binding Protein