Tyrosine-protein kinase Mer (MerTK) (MERTK)

MerTK is a receptor tyrosine kinase of the TAM family (Tyro3–Axl–Mer) that transduces signals from ligands such as Gas6 and Protein S to regulate efferocytosis, immune homeostasis, and cell survival pathways including PI3K/AKT and MAPK. Its extracellular region includes two immunoglobulin-like domains and two fibronectin type III domains, followed by a single-pass transmembrane segment and an intracellular tyrosine kinase domain; proteolytic cleavage generates a soluble Mer that can act as a decoy receptor. Ligand binding induces receptor autophosphorylation and recruitment of adaptors (e.g., GRB2, PLCG2), promoting processes such as macrophage clearance of apoptotic cells, platelet aggregation, and cytoskeletal reorganization; in retinal pigment epithelium it mediates phagocytosis of rod outer segments. MerTK functions as an innate immune checkpoint in macrophages, dampening TLR-driven inflammation via STAT1-dependent induction of SOCS1/3, and is a therapeutic target in cancer; structural studies of its kinase domain support development of small-molecule inhibitors that stabilize inactive conformations or engage the activation loop (type I/1.5).

Other names

MerMer receptor tyrosine kinaseReceptor tyrosine kinase MerTKProto-oncogene c-MerMERMER proto-oncogene, tyrosine kinaseRTK MerTyro3/Axl/Mer family receptor

Small-molecule kinase inhibitors targeting the ATP-binding site/kinase domain of MerTK to block autophosphorylation and downstream signaling (Type I/1.5; inactive-state stabilization reported); Inhibition of MerTK to relieve innate immune checkpoint activity in macrophages, enhancing anti-tumor immunity