Leukocyte migration: dismantling inhibition

A new study demonstrates that the Src-family kinases Fgr and Hck inhibit chemokine signaling in polymorphonuclear leukocytes and dendritic cells by phosphorylation of PIR-B, an inhibitory receptor expressed on leukocytes. In resting cells, PIR-B phosphorylation is constitutive but is decreased transiently by addition of chemokines. In Fgr/Hck-deficient cells, constitutive PIR-B phosphorylation is markedly decreased. These Src-family kinases have a novel role in tonic inhibition of cell activation that must be overcome to allow the phenotypic effects of chemokine signaling through G-protein-coupled receptor ligands.