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American Society of Hematology, Blood, 16(123), p. 2460-2469

DOI: 10.1182/blood-2013-09-528752



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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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TAM receptors (Tyro3, Axl and Mer) belong to a family of Receptor Tyrosine Kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion and migration. TAM receptors can be activated by the vitamin K-dependent proteins Gas6 and protein S. Protein S is more commonly known as an important co-factor for protein C, as well as a direct inhibitor of multiple coagulation factors. To our current knowledge the functions of Gas6 are limited to TAM receptor-activation. When activated, the TAM receptors have effects on primary hemostasis and coagulation, and they display an anti-inflammatory or a pro-inflammatory effect, depending on cell-type. To comprehend the effects that the TAM receptors and their ligands have on hemostasis and inflammation, we compare studies that report the different phenotypes displayed by mice with deficiencies in the genes of this receptor family and its ligands (protein S(+/-), Gas6(-/-), TAM(-/-), and variations to these). In this manner we aim to display which features are attributable to the different ligands. Because of the effects the TAM receptors have on hemostasis, inflammation and cancer growth, their modulation could make interesting therapeutic targets in thrombo-embolic disease, atherosclerosis, sepsis, autoimmune disease and cancer.