Recombinant Mouse Tyrosine-protein kinase Mer (Mertk), partial (Active)

Function

Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. 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. Also plays 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

Subcellular Location

Cell membrane (Single-pass type I membrane protein)

Tissue Specificity

Expressed predominantly in the hematopoietic lineages: macrophages, NK cells, NKT cells, dendritic cells and platelets

Subunit

Interacts (upon activation) with TNK2; stimulates TNK2 autophosphorylation. Interacts (via N-terminus) with extracellular ligands LGALS3, TUB, TULP1 and GAS6. Interacts with VAV1 in a phosphotyrosine-independent manner. Interacts with TIMD4; this interaction enhances TIMD4-mediated efferocytosis (By similarity)

• Graham D.K. et al. Cloning and developmental expression analysis of the murine c-mer tyrosine kinase. — Oncogene (1995)
• Dowds C.A. et al. A cDNA encoding part of a novel putative receptor tyrosine kinase. (JAN-)
• Lu Q. et al. Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. — Nature (1999)
• Georgescu M.M. et al. Biological effects of c-Mer receptor tyrosine kinase in hematopoietic cells depend on the Grb2 binding site in the receptor and activation of NF-kappaB. — Mol. Cell. Biol. (1999)
• Behrens E.M. et al. The mer receptor tyrosine kinase: expression and function suggest a role in innate immunity. — Eur. J. Immunol. (2003)
• Todt J.C. et al. The receptor tyrosine kinase MerTK activates phospholipase C gamma2 during recognition of apoptotic thymocytes by murine macrophages. — J. Leukoc. Biol. (2004)
• Wu Y. et al. A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells. — J. Cell Sci. (2005)
• Tibrewal N. et al. Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-kappaB transcriptional activation. — J. Biol. Chem. (2008)