Tyrosine-protein kinase receptor TYRO3, Axl receptor tyrosine kinase, and Mer tyrosine-protein kinase receptor (collectively known as TAM receptor tyrosine kinases) (TYRO3, Axl, and MerTK (collectively called "TAM" receptors))

The TAM family—comprising Tyrosine-protein kinase receptor TYRO3 (TYRO3), Axl receptor tyrosine kinase (Axl), and Mer tyrosine-protein kinase receptor (MerTK)—forms a distinct subclass of receptor tyrosine kinases characterized by conserved extracellular structures (two immunoglobulin-like domains and two fibronectin III repeats) and a shared intracellular kinase motif. YRO3, Axl, and MerTK are widely expressed across adult tissues and play central roles in the regulation of immune homeostasis, particularly through the clearance of apoptotic cells (efferocytosis), modulation of inflammation, and maintenance of tissue integrity. Pathologically, they are broadly implicated in cancer biology, especially in immune evasion and resistance to anti-cancer therapies, as well as in chronic inflammation, autoimmune disease, neurodegeneration, and disorders of hemostasis. Their primary ligands are the vitamin K–dependent proteins Gas6 and Protein S, with complex ligand binding hierarchies across the three receptors. Due to their multifaceted involvement in disease and pathophysiology, TAM receptors are attractive but complex targets for drug development, although safety concerns remain—especially concerning immune and coagulation homeostasis. Note: For structured databases or detailed analyses, each member—Tyrosine-protein kinase receptor TYRO3, Axl receptor tyrosine kinase, and Mer tyrosine-protein kinase receptor—should be treated as separate canonical entities due to differences in ligand preferences, tissue expression, and certain biological/disease roles.

Other names

TAM receptor familyTAM kinasesTyro3: RSE, BYK, Etk-2, Dtk, Rek, Sky, TifAxl: UFO, Tyro7, JTK11, ARKMerTK: Mer, RP38, c-Eyk, c-mer, Tyro12, MER proto-oncogene

Inhibition of TAM kinase activity (direct kinase inhibition) Disruption of ligand-receptor binding (e.g., ligand traps, mutation of ligand or ligand depletion) Indirect modulation of tumor microenvironment (prevention of M2 macrophage polarization)