HIV TAT Basic Peptide Is Not a High-Affinity Ligand for VEGF Receptor 2
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A. Rubio Demirovic
Abstract
The 'transactivator of transcription' (TAT) protein of human immunodeficiency virus transforms cells in culture and promotes the development of tumors, socalled Kaposi's sarcoma, in AIDS patients. TAT induces growth and differentiation of blood vessels and has been suggested to directly activate VEGF receptor 2 expressed on endothelial cells through a peptide sequence located between amino acids 46 and 64, the so-called basic domain. This peptide mimics many aspects of TAT function when added to endothelial cells, even when expressed in the context of recombinant chimeric proteins. To define the exact sites of interaction between this peptide and VEGF receptor 2 we performed binding studies with recombinant proteins derived from the extracellular ligand binding domain of VEGF receptor 2. These in vitro binding studies showed that the TAT peptide binds with only low specificity to Iglike domain 3 of the receptor, while VEGF interacts with receptor-derived proteins encompassing at least extracellular domains 1 through 3. The original concept that the angiogenic properties of TAT basic peptide result from specific, high-affinity interaction with VEGF receptor 2 must therefore be revised. Apparently this peptide interacts with cells in multiple ways: by directly activating acidic cell surface-exposed receptors, by releasing extracellular matrix-bound growth factors such as bFGF and VEGF which then bind to their cognate receptors, and by activating intracellular signalling molecules with which basic peptide interacts upon translocation into cells.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Mechanisms and Biological Consequences of Nitrosative Stress
- Regulation of the Expression of Inducible Nitric Oxide Synthase
- Nitrosative Stress and Transcription
- Nitric Oxide Signalling with a Special Focus on Lipid-Derived Mediators
- Potential of Embryonic and Adult Stem Cells in vitro
- Ribosomal Tolerance and Peptide Bond Formation
- Transcription of Cathepsin B in Glioma Cells: Regulation by an E-Box Adjacent to the Transcription Initiation Site
- The Catalytically Active Domain in the A Subunit of Calcineurin
- HIV TAT Basic Peptide Is Not a High-Affinity Ligand for VEGF Receptor 2
- Immunogenicity and Protectivity of Plasmodium falciparum EBA-175 Peptide and Its Analog Is Associated with α-Helical Region Shortening and Displacement
- Gene Organization and Molecular Modeling of Copper Amine Oxidase from Aspergillus niger: Re-Evaluation of the Cofactor Structure
- Thermodynamic Analysis of the Dissociation of the Aldolase Tetramer Substituted at One or Both of the Subunit Interfaces
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- Cloning and Characterization of a Transmembrane-Type Serine Protease from Rat Kidney, a New Sodium Channel Activator
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- Suboptimal Action of NF-κB in Fanconi Anemia Cells Results from Low Levels of Thioredoxin
- Modulation of the Activation of Extracellular Signal-Regulated Kinase (ERK) and the Production of Inflammatory Mediators by ADP-Ribosylation Inhibitors
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- Application of the C4'-Alkylated Deoxyribose Primer System (CAPS) in Allele-Specific Real-Time PCR for Increased Selectivity in Discrimination of Single Nucleotide Sequence Variants
