| First Author | Zhang H | Year | 2005 |
| Journal | Immunity | Volume | 22 |
| Issue | 2 | Pages | 235-46 |
| PubMed ID | 15723811 | Mgi Jnum | J:96676 |
| Mgi Id | MGI:3531241 | Doi | 10.1016/j.immuni.2005.01.004 |
| Citation | Zhang H, et al. (2005) The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B. Immunity 22(2):235-46 |
| abstractText | 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. |
