Abstract
Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and have critical roles in the normal physiological function of T lymphocytes. Using an RNA-mediated interference screen, we identified the WNK1 kinase as a regulator of both integrin-mediated adhesion and T cell migration. We found that WNK1 is a negative regulator of integrin-mediated adhesion, whereas it acts as a positive regulator of migration via the kinases OXSR1 and STK39 and the ion co-transporter SLC12A2. WNK1-deficient T cells home less efficiently to lymphoid organs and migrate more slowly through them. Our results reveal that a pathway previously known only to regulate salt homeostasis in the kidney functions to balance T cell adhesion and migration.
MeSH terms
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Animals
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Cell Adhesion / genetics*
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Cell Movement / genetics*
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Cells, Cultured
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Homeostasis
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Ion Transport
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Kidney / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Minor Histocompatibility Antigens / genetics
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Minor Histocompatibility Antigens / metabolism*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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RNA Interference
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Receptors, Lymphocyte Homing / genetics
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Receptors, Lymphocyte Homing / metabolism*
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Solute Carrier Family 12, Member 2 / metabolism
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T-Lymphocytes / physiology*
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WNK Lysine-Deficient Protein Kinase 1
Substances
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Minor Histocompatibility Antigens
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Receptors, Lymphocyte Homing
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Solute Carrier Family 12, Member 2
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Stk39 protein, mouse
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OXSR1 protein, mouse
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Protein Serine-Threonine Kinases
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WNK Lysine-Deficient Protein Kinase 1
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Wnk1 protein, mouse