MERTK
Description
The MERTK (MER proto-oncogene, tyrosine kinase) is a protein-coding gene located on chromosome 2.
The MERTK gene is a member of the TYRO3/AXL/MER (TAM) receptor kinase family and encodes a transmembrane protein with two fibronectin type-III domains, two Ig-like C2-type (immunoglobulin-like) domains, and one tyrosine kinase domain. Mutations in this gene have been linked to disruptions in the retinal pigment epithelium (RPE) phagocytosis pathway and the onset of autosomal recessive retinitis pigmentosa (RP).
MERTK is a receptor tyrosine kinase that transmits signals from the extracellular matrix to the cytoplasm by binding to various ligands including LGALS3, TUB, TULP1, and GAS6. It regulates several physiological processes including cell survival, migration, differentiation, and the phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface triggers autophosphorylation of MERTK on its intracellular domain, providing docking sites for downstream signaling molecules. Following ligand activation, MERTK interacts with GRB2 or PLCG2, leading to the phosphorylation of MAPK1, MAPK2, FAK/PTK2, or RAC1. MERTK signaling is involved in a range of processes like macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization, and engulfment. It functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragment phagocytosis. Additionally, MERTK plays a crucial role in inhibiting Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which specifically induces the production of suppressors of cytokine signaling SOCS1 and SOCS3.
MERTK is also known as MER, RP38, Tyro12, c-Eyk, c-mer.
