PHAGOCYTES G-protein–coupled receptor signaling in Syk-deficient neutrophils and mast cells

The Syk tyrosine kinase is essential for immunoreceptor and multiple integrin functions as well as being implicated in signaling from G-protein–coupled recep-tors (GPCR) in cell lines, transfection systems, and pharmacologic studies. In contrast, using Syk-deficient primary cells, we show here that Syk does not play a major functional role in chemoat-tractant/chemokine signaling in neutro-phils and mast cells. syk/ neutrophils showed normal respiratory burst and de-granulation in response to the bacterial peptide formyl-Met-Leu-Phe (fMLP). The migration of neutrophils toward fMLP was similarly not affected by the syk/ muta-tion. fMLP initiated normal Ca2-signal, activation of the extracellular signal-related kinase (ERK) and p38 mitogen– activated protein (MAP) kinase cascades, and polymerization of cellular actin in the absence of Syk. syk/ and wild-type neu-trophils also responded similarly to LTB4, C5a, and the chemokines macrophage inflammatory protein-1 (MIP-1) or MIP-2, both in functional assays and in intracel-lular signaling mechanisms. Furthermore, bone marrow–derived syk/ mast cells showed normal activation of the Akt, ERK, and p38 MAP kinase pathways when stimulated by the GPCR ligand adeno-sine. We conclude that, in contrast to previous reports, Syk does not play a major role in GPCR signaling. (Blood