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Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-07-2346.
Submitted August 5, 2002
Accepted January 10, 2003
G-protein-coupled receptor signaling in Syk-deficient neutrophils and mast cells
Attila Mocsai, Hong Zhang, Zoltan Jakus, Jiro Kitaura, Toshiaki Kawakami, and Clifford A Lowell*
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
Department of Physiology, Semmelweis University, Budapest, Hungary
Division of Allergy, La Jolla Institute of Allergy and Immunology, San Diego, CA, USA
* Corresponding author; email: clowell{at}cgl.ucsf.edu.
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 pharmacological studies. In contrast, using Syk-deficient primary cells, we show here that Syk does not play a major functional role in chemoattractant/chemokine signaling in neutrophils and mast cells. syk-/- neutrophils showed normal respiratory burst and degranulation in response to the bacterial peptide fMLP. The migration of neutrophils towards fMLP was similarly not affected by the syk-/- mutation. fMLP initiated normal Ca2+-signal, activation of the ERK and p38 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 MIP-1 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.
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