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A Critical Role for Syk in Signal Transduction and Phagocytosis Mediated by Fcγ Receptors on Macrophages
| Content Provider | Scilit |
|---|---|
| Author | Crowley, Mary T. Costello, Patrick S. Fitzer-Attas, Cheryl J. Turner, Martin Meng, Fanying Lowell, Clifford Tybulewicz, Victor DeFranco, Anthony L. |
| Copyright Year | 1997 |
| Description | 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199061/pdf http://jem.rupress.org/content/jem/186/7/1027.full.pdf |
| Ending Page | 1039 |
| Page Count | 13 |
| Starting Page | 1027 |
| DOI | 10.1084/jem.186.7.1027 |
| Journal | The Journal of experimental medicine |
| Issue Number | 7 |
| Volume Number | 186 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 1997-10-06 |
| Access Restriction | Open |
| Subject Keyword | Immunology Phosphorylation Signal Transduction Syk Mediated Phagocytosis Macrophages Derived Fcγr Journal: The Journal of experimental medicine (Vol- 186, Issue- 7) |
| Content Type | Text |
