Binding of Urokinase Plasminogen Activator to gp130 via a Putative Urokinase-Binding Consensus Sequence
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Abstract
Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are instrumental in cellular activities during inflammation, angiogenesis and tumor metastasis. Recent studies suggest that uPA might exert its function on cell proliferation and migration in a uPAR-independent manner or through an adaptor to the uPA-uPAR system. By applying phage display technology, we have identified a putative uPA-binding consensus sequence BXXSSXXB (where B represents a basic amino acid and X represents any amino acid), which has no apparent sequence correlation to uPAR. This uPA-binding motif apparently recognizes the kringle domain of the protease and has an agonistic effect on uPA binding to immobilized uPAR, thereby possibly serving as part of an adaptor component for uPAR signaling. As a result of protein database searches, this motif was found in the extracellular domain of several cell surface proteins, some of which were proposed to be associated with the uPA-uPAR system. Among these, gp130, a common signal transducer for cytokines, was identified as a uPA-binding protein. The specificity of this interaction was demonstrated by inhibition of uPA-binding to immobilized gp130 with soluble gp130. Furthermore, the binding could be partially inhibited by a uPA-binding consensus sequence-containing fusion protein in a dose-dependent manner, with an IC50 of approximately 1 M, indicating that the uPA-binding motif is apparently involved in the uPA-gp130 interaction. The association of gp130 with uPA may link the uPA-uPAR system to various signal transduction pathways.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
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- Obituary
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- Transcriptional Repression of the Human p53 Gene by Hepatitis B Viral Core Protein (HBc) in Human Liver Cells
- Identification of Cytosolic Leucyl Aminopeptidase (EC 3.4.11.1) as the Major Cysteinylglycine-Hydrolysing Activity in Rat Liver
- A Novel Influenza A Virus Activating Enzyme from Porcine Lung: Purification and Characterization
- Binding of Urokinase Plasminogen Activator to gp130 via a Putative Urokinase-Binding Consensus Sequence
- Modifications of Glyceraldehyde-3-Phosphate Dehydrogenase Induced by Increasing Concentrations of Peroxynitrite: Early Recognition by 20S Proteasome
- Different Isoforms of the Non-Integrin Laminin Receptor Are Present in Mouse Brain and Bind PrP
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- Quantitation of Membrane Type Serine Protease 1 (MT-SP1) in Transformed and Normal Cells
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- Cystatins C, E/M and F in Human Pleural Fluids of Patients with Neoplastic and Inflammatory Lung Disorders
- A Homodimeric Sporamin-Type Trypsin Inhibitor with Antiproliferative, HIV Reverse Transcriptase-Inhibitory and Antifungal Activities from Wampee (Clausena lansium) Seeds
- Primary Structure and Reactive Site of a Novel Wheat Proteinase Inhibitor of Subtilisin and Chymotrypsin
- Diverse Enzymatic Specificities of Digestive Proteases, 'Intestains', Enable Colorado Potato Beetle Larvae to Counteract the Potato Defence Mechanism
- Protease Inhibitors Prevent Plasminogen-Mediated, But Not Pemphigus Vulgaris-Induced, Acantholysis in Human Epidermis
- Purification and Primary Structure Determination of Human Lysosomal Dipeptidase
- A Bioinformatic Approach to the Identification of Candidate Genes for the Development of New Cancer Diagnostics
Articles in the same Issue
- Obituary
- Thrombin Signaling in the Brain: The Role of Protease-Activated Receptors
- Transcriptional Repression of the Human p53 Gene by Hepatitis B Viral Core Protein (HBc) in Human Liver Cells
- Identification of Cytosolic Leucyl Aminopeptidase (EC 3.4.11.1) as the Major Cysteinylglycine-Hydrolysing Activity in Rat Liver
- A Novel Influenza A Virus Activating Enzyme from Porcine Lung: Purification and Characterization
- Binding of Urokinase Plasminogen Activator to gp130 via a Putative Urokinase-Binding Consensus Sequence
- Modifications of Glyceraldehyde-3-Phosphate Dehydrogenase Induced by Increasing Concentrations of Peroxynitrite: Early Recognition by 20S Proteasome
- Different Isoforms of the Non-Integrin Laminin Receptor Are Present in Mouse Brain and Bind PrP
- Cell-Type Specific Targeting and Gene Expression Using a Variant of Polyoma VP1 Virus-Like Particles
- Quantitation of Membrane Type Serine Protease 1 (MT-SP1) in Transformed and Normal Cells
- Interaction of Heat Shock Protein 70 Peptide with NK Cells Involves the NK Receptor CD94
- Cystatins C, E/M and F in Human Pleural Fluids of Patients with Neoplastic and Inflammatory Lung Disorders
- A Homodimeric Sporamin-Type Trypsin Inhibitor with Antiproliferative, HIV Reverse Transcriptase-Inhibitory and Antifungal Activities from Wampee (Clausena lansium) Seeds
- Primary Structure and Reactive Site of a Novel Wheat Proteinase Inhibitor of Subtilisin and Chymotrypsin
- Diverse Enzymatic Specificities of Digestive Proteases, 'Intestains', Enable Colorado Potato Beetle Larvae to Counteract the Potato Defence Mechanism
- Protease Inhibitors Prevent Plasminogen-Mediated, But Not Pemphigus Vulgaris-Induced, Acantholysis in Human Epidermis
- Purification and Primary Structure Determination of Human Lysosomal Dipeptidase
- A Bioinformatic Approach to the Identification of Candidate Genes for the Development of New Cancer Diagnostics
