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 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 chemoattractant/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 Ca(2+)-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 LTB(4), C5a, and the chemokines macrophage inflammatory protein-1 (MIP-1)alpha 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.
Mócsai
Attila
A
Department of Laboratory Medicine, University of California, San Francisco, CA 94143-0134, USA.
Zhang
Hong
H
Jakus
Zoltán
Z
Kitaura
Jiro
J
Kawakami
Toshiaki
T
Lowell
Clifford A
CA
D000818:Animals; D004792:Enzyme Precursors / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D019204:GTP-Binding Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D011956:Receptors, Cell Surface / Q000097:blood / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology; D000072377:Syk Kinase
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019204:GTP-Binding Proteins