Toll-Like Receptor 4/Md-2 (TLR4/MD-2) Antibody – Rat Monoclonal

This gene belongs to the evolutionarily-conserved Toll-like receptor family, whose members are type-1 transmembrane proteins that are involved in innate immunity. Toll-like receptors are characterized by an extracellular leucine-rich repeat domain that functions in ligand recognition and an intracellular toll/interleukin-1 receptor-like domain that is crucial for signal transduction. The receptor encoded by this gene mediates the innate immune response to bacterial lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria, through synthesis of pro-inflammatory cytokines and chemokines. In addition, this protein can recognize other pathogens from Gram-negative and Gram-positive bacteria as well as viral components. Mice deficient in this gene display a number of immune response-related phenotypes including hyporesponsiveness to bacterial lipopolysaccharide and increased levels of respiratory syncytial virus compared to controls. [provided by RefSeq, Sep 2015]

TLR4: Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Also involved in LPS- independent inflammatory responses triggered by Ni(2+). These responses require non-conserved histidines and are, therefore, species-specific. Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4. Binding to bacterial LPS leads to homodimerization. Interacts with LY96 via the extracellular domain. Interacts with MYD88 and TIRAP via their respective TIR domains. Interacts with NOX4. Interacts with CNPY3. Interacts with HSP90B1. The interaction with both CNPY3 and HSP90B1 is required for proper folding in the endoplasmic reticulum. Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells. Belongs to the Toll-like receptor family. 3 isoforms of the human protein are produced by alternative splicing.

Protein type: Receptor, misc.; Membrane protein, integral

Cellular Component: cell surface; cytoplasm; external side of plasma membrane; integral to membrane; integral to plasma membrane; intrinsic to plasma membrane; lipid raft; lipopolysaccharide receptor complex; membrane; perinuclear region of cytoplasm; plasma membrane

Molecular Function: lipopolysaccharide binding; lipopolysaccharide receptor activity; phosphoinositide 3-kinase binding; protein binding; receptor activity; transmembrane receptor activity

Biological Process: activation of innate immune response; activation of MAPK activity; activation of NF-kappaB transcription factor; activation of NF-kappaB-inducing kinase; astrocyte development; B cell proliferation during immune response; defense response to Gram-negative bacterium; detection of lipopolysaccharide; I-kappaB phosphorylation; immune system process; inflammatory response; innate immune response; innate immune response-activating signal transduction; interferon-gamma production; interleukin-1 beta secretion; leukotriene metabolic process; lipopolysaccharide-mediated signaling pathway; macrophage activation; mast cell activation; microglial cell activation; MyD88-dependent toll-like receptor signaling pathway; negative regulation of interferon-gamma production; negative regulation of interleukin-17 production; negative regulation of interleukin-23 production; negative regulation of interleukin-6 production; negative regulation of tumor necrosis factor production; positive regulation of apoptosis; positive regulation of B cell proliferation; positive regulation of chemokine production; positive regulation of DNA binding; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of inflammatory response; positive regulation of interferon-alpha production; positive regulation of interferon-beta biosynthetic process; positive regulation of interferon-beta production; positive regulation of interferon-gamma production; positive regulation of interleukin-1 biosynthetic process; positive regulation of interleukin-1 production; positive regulation of interleukin-10 production; positive regulation of interleukin-12 biosynthetic process; positive regulation of interleukin-12 production; positive regulation of interleukin-13 biosynthetic process; positive regulation of interleukin-6 biosynthetic process; positive regulation of interleukin-6 production; positive regulation of interleukin-8 biosynthetic process; positive regulation of interleukin-8 production; positive regulation of JNK cascade; positive regulation of lymphocyte proliferation; positive regulation of MHC class II biosynthetic process; positive regulation of NF-kappaB import into nucleus; positive regulation of nitric oxide biosynthetic process; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of stress-activated MAPK cascade; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; positive regulation of tumor necrosis factor biosynthetic process; positive regulation of tumor necrosis factor production; production of nitric oxide during acute inflammatory response; regulation of cytokine secretion; regulation of dendritic cell cytokine production; regulation of inflammatory response; regulation of sensory perception of pain; response to bacterium; response to ethanol; response to lipopolysaccharide; response to oxidative stress; signal transduction; toll-like receptor 4 signaling pathway; toll-like receptor signaling pathway