BIOMAT Database Logo BIOMAT Database Logo

Tyrosine 67 in the epidermal growth factor-like domain of tissue-type plasminogen activator is important for clearance by a specific hepatic receptor. 1992

R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
Howard Hughes Medical Institute, Dallas, Texas.

Human tissue-type plasminogen activator (t-PA) is cleared rapidly from the circulation by hepatic receptors, one of which recognizes a site in the epidermal growth factor-like domain of the molecule. To define this site more precisely, we have used oligonucleotide-mediated mutagenesis to introduce amino acid substitutions at specific positions located in turns that connect antiparallel beta-sheets in the epidermal growth factor-like domain. Mutated t-PA proteins with amino acid substitutions of the tyrosine residue at position 67 showed markedly lower rates of endocytosis and degradation by cultured cells of the rat hepatoma (H4) line that express a specific receptor for t-PA, and their half-life in the circulation of rats was extended significantly because of a reduction in the rate of the rapid alpha-phase of clearance. The enzymatic properties and fibrinolytic activity of these mutants in vitro were not significantly different from those of wild-type t-PA. We conclude that tyrosine 67 comprises a key determinant in the clearance of t-PA by a specific hepatic receptor.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008114 Liver Neoplasms, Experimental Experimentally induced tumors of the LIVER. Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
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
D009838 Oligodeoxyribonucleotides A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. Oligodeoxynucleotide,Oligodeoxyribonucleotide,Oligodeoxynucleotides
D010959 Tissue Plasminogen Activator A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. Alteplase,Plasminogen Activator, Tissue-Type,T-Plasminogen Activator,Tissue-Type Plasminogen Activator,Actilyse,Activase,Lysatec rt-PA,TTPA,Tisokinase,Tissue Activator D-44,Lysatec rt PA,Lysatec rtPA,Plasminogen Activator, Tissue,Plasminogen Activator, Tissue Type,T Plasminogen Activator,Tissue Activator D 44,Tissue Type Plasminogen Activator
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell

Related Publications

R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
Hepatic clearance of tissue-type plasminogen activator in rats.
October 1985, Thrombosis and haemostasis,
R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
A tissue-type plasminogen activator mutant with prolonged clearance in vivo. Effect of removal of the growth factor domain.
February 1988, The Journal of biological chemistry,
R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
Urokinase-type plasminogen activator-like proteases in teleosts lack genuine receptor-binding epidermal growth factor-like domains.
August 2012, The Journal of biological chemistry,
R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
Urokinase-type plasminogen activator is effective in fibrin clearance in the absence of its receptor or tissue-type plasminogen activator.
June 1996, Proceedings of the National Academy of Sciences of the United States of America,
R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
Clearance receptors for tissue-type plasminogen activator.
August 1994, International journal of hematology,
R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
Demonstration of a specific clearance receptor for tissue-type plasminogen activator on rat Novikoff hepatoma cells.
March 1992, The Journal of biological chemistry,
R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
Yeast expression and phagemid display of the human urokinase plasminogen activator epidermal growth factor-like domain.
May 1995, Protein engineering,
R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
Effects of octreotide on epidermal growth factor receptor, tissue plasminogen activator, and plasminogen activator inhibitor during intraperitoneal adhesion formation.
January 2003, Journal of gastroenterology,
R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
Domain-domain interactions in hybrids of tissue-type plasminogen activator and urokinase-type plasminogen activator.
December 1995, Protein engineering,
R Bassel-Duby, and N Y Jiang, and T Bittick, and E Madison, and D McGookey, and K Orth, and R Shohet, and J Sambrook, and M J Gething
The role of the finger and growth factor domains in the clearance of tissue-type plasminogen activator by hepatocytes.
November 1995, The Journal of biological chemistry,
Copied contents to your clipboard!