| First Author | Gueller S | Year | 2010 |
| Journal | J Leukoc Biol | Volume | 88 |
| Issue | 4 | Pages | 699-706 |
| PubMed ID | 20571037 | Mgi Jnum | J:165616 |
| Mgi Id | MGI:4837817 | Doi | 10.1189/jlb.0309185 |
| Citation | Gueller S, et al. (2010) Adaptor protein Lnk inhibits c-Fms-mediated macrophage function. J Leukoc Biol 88(4):699-706 |
| abstractText | The M-CSFR (c-Fms) participates in proliferation, differentiation, and survival of macrophages and is involved in the regulation of distinct macrophage functions. Interaction with the ligand M-CSF results in phosphorylation of tyrosine residues on c-Fms, thereby creating binding sites for molecules containing SH2 domains. Lnk is a SH2 domain adaptor protein that negatively regulates hematopoietic cytokine receptors. Here, we show that Lnk binds to c-Fms. Biological and functional effects of this interaction were examined in macrophages from Lnk-deficient (KO) and WT mice. Clonogenic assays demonstrated an elevated number of M-CFUs in the bone marrow of Lnk KO mice. Furthermore, the M-CSF-induced phosphorylation of Akt in Lnk KO macrophages was increased and prolonged, whereas phosphorylation of Erk was diminished. Zymosan-stimulated production of ROS was increased dramatically in a M-CSF-dependent manner in Lnk KO macrophages. Lastly, Lnk inhibited M-CSF-induced migration of macrophages. In summary, we show that Lnk binds to c-Fms and can blunt M-CSF stimulation. Modulation of levels of Lnk in macrophages may provide a unique therapeutic approach to increase innate host defenses. |
