Endothelin suppresses cell migration via the JNK signaling pathway in a manner dependent upon Src kinase, Rac1, and Cdc42.
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.
Yamauchi
Junji
J
Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, 630-0101, Nara, Japan. junyama@bs.aist-nara.ac.jp
Miyamoto
Yuki
Y
Kokubu
Hiroshi
H
Nishii
Hiroko
H
Okamoto
Miyuki
M
Sugawara
Yo
Y
Hirasawa
Akira
A
Tsujimoto
Gozoh
G
Itoh
Hiroshi
H
D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000187:drug effects / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000187:drug effects / Q000378:metabolism*; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism*
D016232:Endothelins; D019061:src-Family Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein