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

Attila Mócsai, Hong Zhang, Zoltán Jakus, Jiro Kitaura, Toshiaki Kawakami, Clifford A. Lowell

Research output: Contribution to journalArticle

88 Citations (Scopus)


The Syk tyrosine kinase is essential for immunoreceptor and multiple integrin functions as well as being implicated in signaling from G-protein-coupled receptors (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 chemo-attractant/chemokine signaling in neutrophils and mast cells. syk-/- neutrophils showed normal respiratory burst and degranulation in response to the bacterial peptide formyl-Met-Leu-Phe (fMLP). The migration of neutrophils toward fMLP was similarly not affected by the syk-/- mutation. 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 neutrophils also responded similarly to LTB4, C5a, and the chemokines macrophage inflammatory protein-1 (MIP-1)α or MIP-2, both in functional assays and in intracellular 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 adenosine. We conclude that, in contrast to previous reports, Syk does not play a major role in GPCR signaling.

Original languageEnglish
Pages (from-to)4155-4163
Number of pages9
Issue number10
Publication statusPublished - May 15 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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