2. Academic Validation
  3. The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B

The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B

  • Immunity. 2005 Feb;22(2):235-46. doi: 10.1016/j.immuni.2005.01.004.
Hong Zhang 1,  Fanying Meng,  Ching-Liang Chu,  Toshiyuki Takai,  Clifford A Lowell
Affiliations

Affiliation

  • 1 Department of Laboratory Medicine , University of California, San Francisco , San Francisco, California 94143, USA.
PMID: 15723811 DOI: 10.1016/j.immuni.2005.01.004
Abstract

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.

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