Tyrosine-protein kinase receptor Axl and Tyrosine-protein kinase Mer (MerTK) (Axl, MerTK)

The **TAM family** comprises three closely related **receptor tyrosine kinases**—Tyro3, Axl (**Axl receptor tyrosine kinase**), and Mer (**Tyrosine-protein kinase Mer**, also known as **MerTK**)—that share structural features including an extracellular domain with immunoglobulin-like motifs and a conserved intracellular tyrosine kinase domain. Their primary ligands are the vitamin K–dependent proteins Gas6 and Protein S. These receptors play critical roles across multiple biological systems: *In the immune system*, they mediate recognition/phagocytosis of apoptotic cells by macrophages via binding to phosphatidylserine on dying cells through their ligands. They also act as negative regulators that suppress excessive inflammatory responses after innate immune activation. *In cancer*, both AXL and MERTK are frequently overexpressed across a wide range of tumors where they promote tumor cell survival/proliferation/motility/metastasis while contributing to chemoresistance. Their inhibition is being explored therapeutically both for direct anti-tumor effects and enhancement of anti-tumor immunity. *In other tissues*, TAM kinases regulate processes like blood clot stabilization/hemostasis via effects on platelets/endothelial cells; their dysfunction is linked with coagulopathies. Because these receptors have pleiotropic functions—including neural development/myelination/cell migration—they are implicated not only in cancer but also autoimmune diseases/neurodegeneration/inflammatory conditions/coagulopathies. Drugs targeting these molecules aim either at blocking oncogenic signaling or modulating immune responses depending on context.

Other names

Axl receptor tyrosine kinaseMERTK (c-Mer proto-oncogene tyrosine kinase)TAM family kinases (when referring to the group including Tyro3, Axl, and MerTK)Receptor protein-tyrosine kinasesc-Mer tyrosine kinase

- Inhibition of receptor autophosphorylation blocks downstream signaling pathways such as PI3K-Akt and MAPKs. - Suppression of cell survival/proliferation signals. - Enhancement of anti-tumor immunity by reducing immunosuppressive effects mediated by TAM signaling. - Impairment of phagocytic clearance functions in macrophages when inhibited.