The Src Family Kinases Hck and Fgr Negatively Regulate Neutrophil and Dendritic Cell Chemokine Signaling via PIR-B
Copyright policy )The Src Family Kinases Hck and Fgr Negatively Regulate Neutrophil and Dendritic Cell Chemokine Signaling via PIR-B
In classical descriptions of leukocyte chemokine signaling, Src family kinases are thought to function in a positive fashion by coupling receptor associated Galpha subunits to downstream mitogen activated protein (MAP) kinase activation. However, neutrophils derived from hck-/-fgr-/- mice and dendritic cells (DCs) from fgr-/- animals manifested significantly higher intracellular signaling (Ca2+ flux, MAP kinase activation, actin polymerization) and functional responses (chemotaxis in vitro and migration in vivo) to a number of different chemokines. These kinases may mediate their effect through the inhibitory receptor PIR-B since neutrophils and DCs from pir-b-/- mice were also hyperresponsive to chemokine stimulation. In wild-type (wt) cells dephosphorylation of PIR-B was associated with maximal chemokine signaling, whereas in hck-/-fgr-/- cells PIR-B was unphosphorylated. These data support a model in which the Src family kinases Hck and Fgr function as negative regulators of myeloid cell chemokine signaling by maintaining the tonic phosphorylation of PIR-B.
- University of California, San Francisco United States
- Tohoku University Japan
Neutrophils, Immunology, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Mice, Cell Movement, Proto-Oncogene Proteins, Immunology and Allergy, Animals, Phosphorylation, Receptors, Immunologic, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Intracellular Signaling Peptides and Proteins, Dendritic Cells, Macrophage Inflammatory Proteins, Protein-Tyrosine Kinases, Infectious Diseases, Gene Expression Regulation, Mutation, Proto-Oncogene Proteins c-hck, Leukocyte Common Antigens, Chemokines, Protein Tyrosine Phosphatases, Signal Transduction
Neutrophils, Immunology, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Mice, Cell Movement, Proto-Oncogene Proteins, Immunology and Allergy, Animals, Phosphorylation, Receptors, Immunologic, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Intracellular Signaling Peptides and Proteins, Dendritic Cells, Macrophage Inflammatory Proteins, Protein-Tyrosine Kinases, Infectious Diseases, Gene Expression Regulation, Mutation, Proto-Oncogene Proteins c-hck, Leukocyte Common Antigens, Chemokines, Protein Tyrosine Phosphatases, Signal Transduction
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