Biomaterial Database

Turnover of thrombomodulin at the cell surface occurs at a similar rate to receptors that are not actively internalized. 1998

M Chu, and C H Bird, and M Teasdale, and P I Bird

Department of Medicine, Monash Medical School, Box Hill Hospital, Australia.

Loss of thrombomodulin (TM) from the endothelial cell surface is thought to contribute to thrombosis encountered in malignant and inflammatory disease. Internalization or endocytosis of TM from the cell surface has been proposed to be one mechanism by which TM levels are reduced. Previous work has led to a view that TM is rapidly internalized using a non-conventional pathway, under the direction of a signal motif in its extracellular domain. This is contrary to the clathrin-dependent route taken by most rapidly internalized receptors that possess signals in their cytoplasmic domains. However the internalization rate of TM has never been directly compared to known internalizing or non-internalizing molecules. Here we show that the rate and amount of uptake of TM (5-10% per hour) is indistinguishable from the non-internalizing influenza virus haemagglutinin (HA), and is considerably less than the actively internalizing low density lipoprotein receptor, which reaches a steady state of approximately 50% internalized in 15 min. The low level rate of TM and HA internalization observed is comparable to the rate of normal plasma membrane turnover. Furthermore, this uptake of TM does not require a signal in its extracellular domain.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011973	Receptors, LDL	Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.	LDL Receptors,Lipoprotein LDL Receptors,Receptors, Low Density Lipoprotein,LDL Receptor,LDL Receptors, Lipoprotein,Low Density Lipoprotein Receptor,Low Density Lipoprotein Receptors,Receptors, Lipoprotein, LDL,Receptor, LDL,Receptors, Lipoprotein LDL
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000937	Antigen-Antibody Reactions	The processes triggered by interactions of ANTIBODIES with their ANTIGENS.	Antigen Antibody Reactions,Antigen-Antibody Reaction,Reaction, Antigen-Antibody,Reactions, Antigen-Antibody
D017261	Glycosylphosphatidylinositols	Compounds containing carbohydrate or glycosyl groups linked to phosphatidylinositols. They anchor GPI-LINKED PROTEINS or polysaccharides to cell membranes.	GPI Membrane Anchor,GPI Membrane Anchors,Glycosyl-Phosphatidylinositol Membrane Protein Anchor,Glycosylated Phosphatidylinositol,Glycosylphosphatidylinositol Anchor,Glycosylphosphatidylinositol Anchors,Phosphatidylinositol Glycan,Gly-PtdIns,Glycoinositol Phospholipid Membrane Anchor,Glycosyl-Phosphatidylinositol,Glycosyl-Phosphatidylinositol Membrane Protein Anchors,Glycosylated Phosphatidylinositols,Glycosylphosphatidylinositol,Glycosylphosphatidylinositol Linkage,PI-Glycan,Anchor, GPI Membrane,Anchor, Glycosylphosphatidylinositol,Anchors, GPI Membrane,Anchors, Glycosylphosphatidylinositol,Glycan, Phosphatidylinositol,Glycosyl Phosphatidylinositol,Glycosyl Phosphatidylinositol Membrane Protein Anchor,Glycosyl Phosphatidylinositol Membrane Protein Anchors,Linkage, Glycosylphosphatidylinositol,Membrane Anchor, GPI,Membrane Anchors, GPI,PI Glycan,Phosphatidylinositol, Glycosylated,Phosphatidylinositols, Glycosylated
D017434	Protein Structure, Tertiary	The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure.	Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures
D018180	Thrombomodulin	A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.