Tyrosine-protein Kinase Mer, also known as c-Mer and MerTK, is a member of the receptor tyrosine kinase subfamily TAM (Tyro3, Axl, and Mer). Similar to Axl and Tyro3, the extracelluar domain of Mer contains two Ig-like motifs and two fibronectin type III motifs. Mer is not expressed in normal B- and T-cells but expressed in neoplastic B- and T-cell lines . It is also show higher expression in immunosuppressive M2‑like macrophages. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.Mer is known to bind Gas6, Protein S, Tubby, Tubby-like protein 1 (Tulp1), and Galectin-3. Upon binding ligands via the Ig-like motif, Mer is dimerized to trans-autophosphorylate the kinase domain to induce downstream signaling. It has been shown that Mer signaling in macrophages induces M2 polarization, which promote tumor growth, metastasis and evasion of anti-tumor immunity in tumor microenviroment. Inhibition of Mer, especially on leukocytes and macrophages, is an effective anti-cancer therapy.
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