Adaptor protein Lnk inhibits c-Fms-mediated macrophage function

Saskia Gueller, Helen S. Goodridge, Birte Niebuhr, Hongtao Xing, Maya Koren-Michowitz, Hubert Serve, David M. Underhill, Christian H. Brandts, H. Phillip Koeffler

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)699-706
Number of pages8
JournalJournal of Leukocyte Biology
Issue number4
StatePublished - Oct 2010
Externally publishedYes


  • Cytokine
  • Migration
  • Receptor tyrosine kinase
  • ROS
  • Signaling


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