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A critical role for Syk in signal transduction and phagocytosis mediated by Fc gamma receptors on macrophages

Title: A critical role for Syk in signal transduction and phagocytosis mediated by Fc gamma receptors on macrophages
Authors: Crowley, MT
Costello, PS
FitzerAttas, CJ
Turner, M
Meng, FY
Lowell, C
Tybulewicz, VLJ
DeFranco, AL
Item Type: Journal Article
Abstract: Receptors on macrophages for the Fc region of IgG (FcγR) mediate a number of responses important for host immunity. Signaling events necessary for these responses are likely initiated by the activation of Src-family and Syk-family tyrosine kinases after FcγR cross-linking. Macrophages derived from Syk-deficient (Syk−) mice were defective in phagocytosis of particles bound by FcγRs, as well as in many FcγR-induced signaling events, including tyrosine phosphorylation of a number of cellular substrates and activation of MAP kinases. In contrast, Syk− macrophages exhibited normal responses to another potent macrophage stimulus, lipopolysaccharide. Phagocytosis of latex beads and Escherichia coli bacteria was also not affected. Syk− macrophages exhibited formation of polymerized actin structures opposing particles bound to the cells by FcγRs (actin cups), but failed to proceed to internalization. Interestingly, inhibitors of phosphatidylinositol 3-kinase also blocked FcγR-mediated phagocytosis at this stage. Thus, PI 3-kinase may participate in a Syk-dependent signaling pathway critical for FcγR-mediated phagocytosis. Macrophages derived from mice deficient for the three members of the Src-family of kinases expressed in these cells, Hck, Fgr, and Lyn, exhibited poor Syk activation upon FcγR engagement, accompanied by a delay in FcγR-mediated phagocytosis. These observations demonstrate that Syk is critical for FcγR-mediated phagocytosis, as well as for signal transduction in macrophages. Additionally, our findings provide evidence to support a model of sequential tyrosine kinase activation by FcγR's analogous to models of signaling by the B and T cell antigen receptors.
Issue Date: 6-Oct-1997
Date of Acceptance: 29-Jul-1997
URI: http://hdl.handle.net/10044/1/57997
DOI: https://dx.doi.org/10.1084/jem.186.7.1027
ISSN: 0022-1007
Publisher: Rockefeller University Press
Start Page: 1027
End Page: 1039
Journal / Book Title: JOURNAL OF EXPERIMENTAL MEDICINE
Volume: 186
Issue: 7
Copyright Statement: © 1997 Rockefeller University Press
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
PROTEIN-TYROSINE KINASE
PHOSPHOINOSITIDE 3-KINASE
ANTIGEN RECEPTOR
HUMAN MONOCYTES
B-LYMPHOCYTES
PHOSPHORYLATION
ACTIVATION
LIPOPOLYSACCHARIDE
STIMULATION
P72(SYK)
Androstadienes
Animals
Calcium-Calmodulin-Dependent Protein Kinases
Cytokines
Enzyme Precursors
Erythrocytes
Intracellular Signaling Peptides and Proteins
Lipopolysaccharides
Liver
Macrophages
Mice
Mice, Knockout
Microspheres
Phagocytosis
Phosphatidylinositol 3-Kinases
Phosphorylation
Protein-Tyrosine Kinases
Receptors, IgG
Signal Transduction
Syk Kinase
src-Family Kinases
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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