Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways (    , ). At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) . Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+) . Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response ( , ). Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production . In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade . In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86 . Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway . In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14-dependent manner (, ). Required for the migration-promoting effects of ZG16B/PAUF on pancreatic cancer cells.
Subcellular locations: Cell membrane, Early endosome, Cell projection, Ruffle
Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis . Colocalizes with RFTN1 at cell membrane and then together with RFTN1 moves to endosomes, upon lipopolysaccharide stimulation. Co-localizes with ZG16B/PAUF at the cell membrane of pancreatic cancer cells .
Highly expressed in placenta, spleen and peripheral blood leukocytes (, ). Detected in monocytes, macrophages, dendritic cells and several types of T-cells (, ). Expressed in pancreatic cancer cells but not in normal pancreatic cells (at protein level) .