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Nat Immunol. 2014 Oct;15(10):920-8. doi: 10.1038/ni.2986. Epub 2014 Sep 7.

Diversification of TAM receptor tyrosine kinase function.

Author information

1
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.
2
MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
3
1] Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA. [2] Immunobiology and Microbial Pathogenesis Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.

Abstract

The clearance of apoptotic cells is critical for both tissue homeostasis and the resolution of inflammation. We found that the TAM receptor tyrosine kinases Axl and Mer had distinct roles as phagocytic receptors in these two settings, in which they exhibited divergent expression, regulation and activity. Mer acted as a tolerogenic receptor in resting macrophages and during immunosuppression. In contrast, Axl was an inflammatory response receptor whose expression was induced by proinflammatory stimuli. Axl and Mer differed in their ligand specificities, ligand-receptor complex formation in tissues, and receptor shedding upon activation. These differences notwithstanding, phagocytosis by either protein was strictly dependent on receptor activation triggered by bridging of TAM receptor-ligand complexes to the 'eat-me' signal phosphatidylserine on the surface of apoptotic cells.

Comment in

PMID:
25194421
PMCID:
PMC4169336
DOI:
10.1038/ni.2986
[Indexed for MEDLINE]
Free PMC Article
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