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TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis

Jonathan H M van der Meer1, Tom van der Poll, Cornelis van 't Veer

  • 1Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Blood
|March 6, 2014
PubMed

Insights

The TAM receptor system, including Tyro3, Axl, and Mer, influences blood clotting and inflammation. Understanding their ligands, Gas6 and Protein S, is key for potential therapies in various diseases.

Area of Science:

  • Biochemistry
  • Immunology
  • Molecular Biology

Background:

  • TAM receptors (Tyro3, Axl, Mer) are receptor tyrosine kinases involved in hemostasis, inflammation, and cell functions.
  • They are activated by vitamin K-dependent proteins Gas6 and Protein S.
  • Protein S also acts as a cofactor for protein C and inhibits coagulation factors.

Purpose of the Study:

  • To elucidate the distinct roles of TAM receptors and their ligands (Gas6, Protein S) in hemostasis and inflammation.
  • To compare phenotypes of gene-deficient mice to attribute functions to specific ligands.

Main Methods:

  • Comparative analysis of studies on gene-deficient mice (Protein S(+/-), Gas6(-/-), TAM(-/-)).
  • Review of existing literature on TAM receptor and ligand functions.

Main Results:

  • TAM receptor activation impacts primary hemostasis and coagulation.
  • Activated TAM receptors can exert either anti-inflammatory or pro-inflammatory effects depending on the cell type.
  • Ligand-specific contributions to TAM receptor signaling pathways were investigated.

Conclusions:

  • The TAM receptor system significantly influences hemostasis and inflammation.
  • Gas6 and Protein S play distinct roles in activating TAM receptors.
  • Modulating TAM receptors offers potential therapeutic strategies for thromboembolic disorders, atherosclerosis, sepsis, autoimmune diseases, and cancer.

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