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Random Peptide Bacteriophage Display as a Probe for Urokinase Receptor Ligands
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Susan Fong
Veröffentlicht/Copyright:
1. Juni 2005
Abstract
The urokinase receptor is a multifunctional protein that plays a central role in cell surface plasminogen activation, cell migration, and cell adhesion. We previously demonstrated that high affinity peptide ligands for the urokinase receptor, which are urokinase competitors, can be obtained from a 15mer peptide library (Goodson et al., 1994). In order to probe for additional urokinase receptor binding sites we affinity selected the same bacteriophage library on complexes of soluble urokinase receptor (suPAR) and the receptor binding domain of urokinase, residues 1 48 (uPA1 48). Bacteriophage were isolated which bound to suPAR and suPAR:uPA1 48 complexes with high yield. The peptide sequences encoded by these bacteriophage were distinct from those obtained previously on urokinase receptor expressing cells, and comprise two groups based upon effects on su PAR:1-anilino-8-napthalene sulfonate (ANS) fluorescence, and vitronectin binding competition. Alanine scanning mutagensis of the soluble peptides was used to define minimal regions and key residues for suPAR binding by competition with the parent bacteriophage. A comparison of these results with sequences of domains of both vitronectin and integrin αchains, which have been reported to be important for urokinase receptor binding, suggests that the homology with the peptide sequences selected is functionally significant.
:
Published Online: 2005-06-01
Published in Print: 2002-01-23
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
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Artikel in diesem Heft
- Non-Enzymatic Activities of Proteases: From Scepticism to Reality
- The Urokinase Plasminogen Activator Receptor in the Regulation of the Actin Cytoskeleton and Cell Motility
- The Molecular Basis for Anti-Proteolytic and Non-Proteolytic Functions of Plasminogen Activator Inhibitor Type-1: Roles of the Reactive Centre Loop, the Shutter Region, the Flexible Joint Region and the Small Serpin Fragment
- Nervous System Pathology: The Fibrin Perspective
- Post-Transcriptional Regulation of Gene Expression in the Plasminogen Activation System
- Role of Myofibroblasts at the Invasion Front
- Transmodulation of Cell Surface Regulatory Molecules via Ectodomain Shedding
- The Plasminogen Activating System in Periodontal Health and Disease
- Apolipoprotein(a): Structure-Function Relationship at the Lysine-Binding Site and Plasminogen Activator Cleavage Site
- Anti-Invasive Effects of Green Tea Polyphenol EpiGalloCatechin-3-Gallate (EGCG), a Natural Inhibitor of Metallo and Serine Proteases
- Inhibition of Receptor-Dependent Urokinase Signaling by Specific Ser to Glu Substitutions
- Activation of p38 MAP-Kinase and Caldesmon Phosphorylation Are Essential for Urokinase-Induced Human Smooth Muscle Cell Migration
- Growth Factor-Dependent Proliferation and Invasion of Muscle Satellite Cells Require the Cell-Associated Fibrinolytic System
- The Col-1 Module of Human Matrix Metalloproteinase-2 (MMP-2): Structural/Functional Relatedness between Gelatin-Binding Fibronectin Type II Modules and Lysine-Binding Kringle Domains
- Random Peptide Bacteriophage Display as a Probe for Urokinase Receptor Ligands
- Plasmin Produces an E-Cadherin Fragment That Stimulates Cancer Cell Invasion
- The Role of Proteases in Fibronectin Matrix Remodeling in Thyroid Epithelial Cell Monolayer Cultures
- Induction of Fibronectin mRNA by Urokinase- and Tissue-Type Plasminogen Activator in Human Skin Fibroblasts: Differential Role of u-PA and t-PA at the Fibronectin Protein Level
- Platelet Activating Factor Inhibits the Expression of Matrix Metalloproteinases and Affects Invasiveness and Differentiation in a System of Human Neuroblastoma Clones
- UVA Light Stimulates the Production of Cathepsin G and Elastase-Like Enzymes by Dermal Fibroblasts: A Possible Contribution to the Remodeling of Elastotic Areas in Sun-Damaged Skin
- uPA-Silica-Particles (SP-uPA): A Novel Analytical System to Investigate uPA-uPAR Interaction and to Test Synthetic uPAR Antagonists as Potential Cancer Therapeutics
- Monocyte-Expressed Urokinase Regulates Human Vascular Smooth Muscle Cell Migration in a Coculture Model
- Distinct Expression Pattern of Two Related Human Proteins Containing Multiple Types of Protease-Inhibitory Modules
- Osteopontin Modulates Prostate Carcinoma Invasive Capacity through RGD-Dependent Upregulation of Plasminogen Activators
- Expression of Matrix Metalloproteases (MMP-2, MT1-MMP) and Their Tissue Inhibitor (TIMP-2) by Rat Sertoli Cells in Culture: Implications for Spermatogenesis
Artikel in diesem Heft
- Non-Enzymatic Activities of Proteases: From Scepticism to Reality
- The Urokinase Plasminogen Activator Receptor in the Regulation of the Actin Cytoskeleton and Cell Motility
- The Molecular Basis for Anti-Proteolytic and Non-Proteolytic Functions of Plasminogen Activator Inhibitor Type-1: Roles of the Reactive Centre Loop, the Shutter Region, the Flexible Joint Region and the Small Serpin Fragment
- Nervous System Pathology: The Fibrin Perspective
- Post-Transcriptional Regulation of Gene Expression in the Plasminogen Activation System
- Role of Myofibroblasts at the Invasion Front
- Transmodulation of Cell Surface Regulatory Molecules via Ectodomain Shedding
- The Plasminogen Activating System in Periodontal Health and Disease
- Apolipoprotein(a): Structure-Function Relationship at the Lysine-Binding Site and Plasminogen Activator Cleavage Site
- Anti-Invasive Effects of Green Tea Polyphenol EpiGalloCatechin-3-Gallate (EGCG), a Natural Inhibitor of Metallo and Serine Proteases
- Inhibition of Receptor-Dependent Urokinase Signaling by Specific Ser to Glu Substitutions
- Activation of p38 MAP-Kinase and Caldesmon Phosphorylation Are Essential for Urokinase-Induced Human Smooth Muscle Cell Migration
- Growth Factor-Dependent Proliferation and Invasion of Muscle Satellite Cells Require the Cell-Associated Fibrinolytic System
- The Col-1 Module of Human Matrix Metalloproteinase-2 (MMP-2): Structural/Functional Relatedness between Gelatin-Binding Fibronectin Type II Modules and Lysine-Binding Kringle Domains
- Random Peptide Bacteriophage Display as a Probe for Urokinase Receptor Ligands
- Plasmin Produces an E-Cadherin Fragment That Stimulates Cancer Cell Invasion
- The Role of Proteases in Fibronectin Matrix Remodeling in Thyroid Epithelial Cell Monolayer Cultures
- Induction of Fibronectin mRNA by Urokinase- and Tissue-Type Plasminogen Activator in Human Skin Fibroblasts: Differential Role of u-PA and t-PA at the Fibronectin Protein Level
- Platelet Activating Factor Inhibits the Expression of Matrix Metalloproteinases and Affects Invasiveness and Differentiation in a System of Human Neuroblastoma Clones
- UVA Light Stimulates the Production of Cathepsin G and Elastase-Like Enzymes by Dermal Fibroblasts: A Possible Contribution to the Remodeling of Elastotic Areas in Sun-Damaged Skin
- uPA-Silica-Particles (SP-uPA): A Novel Analytical System to Investigate uPA-uPAR Interaction and to Test Synthetic uPAR Antagonists as Potential Cancer Therapeutics
- Monocyte-Expressed Urokinase Regulates Human Vascular Smooth Muscle Cell Migration in a Coculture Model
- Distinct Expression Pattern of Two Related Human Proteins Containing Multiple Types of Protease-Inhibitory Modules
- Osteopontin Modulates Prostate Carcinoma Invasive Capacity through RGD-Dependent Upregulation of Plasminogen Activators
- Expression of Matrix Metalloproteases (MMP-2, MT1-MMP) and Their Tissue Inhibitor (TIMP-2) by Rat Sertoli Cells in Culture: Implications for Spermatogenesis
