Tyrosine-protein kinase receptor TYRO3, AXL, and MER (collectively: TAM receptor tyrosine kinases) (TAM kinases)

The **TAM kinases** (Tyro3, Axl, and Mer) are a distinct subfamily of **receptor tyrosine kinases (RTKs)** characterized by a specific extracellular domain structure (two immunoglobulin-like domains and two fibronectin type III repeats) and an intracellular kinase domain[3][7]. They use vitamin K-dependent ligands, notably **growth arrest-specific protein 6 (Gas6)** and **protein S**, which mediate receptor activation through ligand-induced dimerization and autophosphorylation[1][2][3][6]. TAM kinases regulate fundamental cellular processes including signal transduction, cell proliferation, migration, immune suppression, and apoptotic cell clearance, and play particularly important roles in the nervous and immune systems[1][2][4][5][7]. Overexpression or dysregulation of TAM receptors contributes to various diseases, most notably cancer, where they promote tumor survival, metastasis, and resistance to treatment, and play an immunosuppressive role in the tumor microenvironment[2][4][6][8]. Therapies targeting TAM kinases—especially AXL—include small-molecule inhibitors, monoclonal antibodies, antibody-drug conjugates, and CAR-T programs, with many agents now in preclinical or clinical evaluation[6][8]. Safety concerns relate to the risk of triggering autoimmunity or interfering with normal clearance of apoptotic cells, given the essential physiological roles of these receptors[5][7]. TAM kinases act as both direct and immune-modulating therapeutic targets in oncology but also contribute to infectious disease by facilitating virus entry into cells[6].

Other names

TAM kinasesTAM receptor tyrosine kinasesTAM RTKsTYRO3, AXL, and MERTK (gene/protein names: Tyro3, Axl, Mer, MERTK)Sometimes referred individually: "Tyro3"Sometimes referred individually: "Axl"Sometimes referred individually: "MerTK"

Inhibition of kinase activity (blocking phosphorylation and downstream signaling). Inhibition of receptor dimerization (prevent signal initiation). Disruption of ligand–receptor interaction (e.g., blocking Gas6 and protein S binding). Suppression of tumor cell survival, proliferation, migration, invasion, EMT, and stemness. Reduction of immunosuppression in the tumor microenvironment (augmentation of antitumour immunity).