Rho kinase is required for CCR7-mediated polarization and chemotaxis of T lymphocytes.
We studied the role of Rho kinase and extracellular signal-regulated kinase (ERK)-2 in the polarization and migration of T lymphocytes in response to the CCR7 ligands EBI1 ligand chemokine (ELC; CCL19) and secondary lymphoid-tissue chemokine (SLC; CCL21). Both Rho kinase protein isoforms are expressed in T lymphocytes. Inhibition of the Rho kinases with Y-27632 strongly inhibited SLC- and ELC-induced polarized morphology and chemotaxis of T lymphocytes. Although the chemokines induced ERK-2 activation, the blockade of this signaling pathway showed no effect on polarization and migration. This study indicates an important role of Rho kinase in CCR7-mediated polarization and migration of T lymphocytes, whereas ERK-2 is not involved in these processes.
Theodor Kocher Institute, P.O. Box, CH-3000 9 Bern, Switzerland.
Giuseppe
G
Bardi
Verena
V
Niggli
Pius
P
Loetscher
D000577:Amides / Q000494:pharmacology; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D054460:rho-Associated Kinases
D000577:Amides; C515370:CCR7 protein, human; D018925:Chemokines; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D019950:Mitogen-Activated Protein Kinase 1