Molecular Cloning and Characterization of Endosialin, a C-type Lectin-like Cell Surface Receptor of Tumor Endothelium
| Autor: | Horst Ahorn, Martin Lenter, John Edward Park, Hans-Peter Rodi, Andreas Koehler, Frank Eisenhaber, Wolfgang J. Rettig, Pilar Garin-Chesa, Sven Christian |
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| Rok vydání: | 2001 |
| Předmět: |
Signal peptide
Cytoplasm Silver Staining DNA Complementary Databases Factual EGF-like domain Thrombomodulin Molecular Sequence Data Protein Sorting Signals Biology Transfection Biochemistry Endosialin Antigens CD Antigens Neoplasm C-type lectin Cell surface receptor Lectins Complementary DNA Tumor Cells Cultured Humans Amino Acid Sequence Endothelium Cloning Molecular Molecular Biology Peptide sequence Expressed Sequence Tags Base Sequence Sequence Homology Amino Acid Cell Membrane Membrane Proteins Cell Biology Blotting Northern Immunohistochemistry Precipitin Tests Molecular biology Neoplasm Proteins Protein Structure Tertiary Transmembrane domain HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 276:7408-7414 |
| ISSN: | 0021-9258 |
| Popis: | Endosialin, the antigen identified with monoclonal antibody FB5, is a highly restricted 165-kDa cell surface glycoprotein expressed by tumor blood vessel endothelium in a broad range of human cancers but not detected in blood vessels or other cell types in many normal tissues. Functional analysis of endosialin has been hampered by a lack of information about its molecular structure. In this study, we describe the purification and partial amino acid sequencing of endosialin, leading to the cloning of a full-length cDNA with an open reading frame of 2274 base pairs. The endosialin cDNA encodes a type I membrane protein of 757 amino acids with a predicted molecular mass of 80.9 kDa. The sequence matches with an expressed sequence tag of unknown function in public data bases, named TEM1, which was independently linked to tumor endothelium by serial analysis of gene expression profiling. Bioinformatic evaluation classifies endosialin as a C-type lectin-like protein, composed of a signal leader peptide, five globular extracellular domains (including a C-type lectin domain, one domain with similarity to the Sushi/ccp/scr pattern, and three EGF repeats), followed by a mucin-like region, a transmembrane segment, and a short cytoplasmic tail. Carbohydrate analysis shows that the endosialin core protein carries abundantly sialylated, O-linked oligosaccharides and is sensitive to O-sialoglycoprotein endopeptidase, placing it in the group of sialomucin-like molecules. The N-terminal 360 amino acids of endosialin show homology to thrombomodulin, a receptor involved in regulating blood coagulation, and to complement receptor C1qRp. This structural kinship may indicate a function for endosialin as a tumor endothelial receptor for as yet unknown ligands, a notion now amenable to molecular investigation. |
| Databáze: | OpenAIRE |
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