Adaptor protein Lnk inhibits c‐Fms‐mediated macrophage function
In: Journal of Leukocyte Biology, Jg. 88 (2010-10-01), Heft 4, S. 699-706
Online
serialPeriodical
Zugriff:
Lnk physically interacts with c‐Fms and blunts its activity in‐cluding proliferation of macrophage progenitor cells, M‐CSF stimulated migration, and generaton of ROS. 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.
Titel: |
Adaptor protein Lnk inhibits c‐Fms‐mediated macrophage function
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Autor/in / Beteiligte Person: | Gueller, Saskia ; Goodridge, Helen S. ; Niebuhr, Birte ; Xing, Hongtao ; Koren‐Michowitz, Maya ; Serve, Hubert ; Underhill, David M. ; Brandts, Christian H. ; Koeffler, H. Phillip |
Link: | |
Zeitschrift: | Journal of Leukocyte Biology, Jg. 88 (2010-10-01), Heft 4, S. 699-706 |
Veröffentlichung: | 2010 |
Medientyp: | serialPeriodical |
ISSN: | 0741-5400 (print) ; 1938-3673 (print) |
DOI: | 10.1189/jlb.0309185 |
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