| The amino terminal lectin-like domain of thrombomodulin is required for constitutive endocytosis. | |
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MedLine Citation:
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PMID: 9002969 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thrombomodulin (TM) is a multidomain protein that serves as a cofactor in a major natural anticoagulant system. To further characterize the structure-function of TM, we have transfected COS cells with different truncated forms of TM. In the first form, COS cells expressing TM that lacks the putative signal peptide (17 residues); the lectin-like, hydrophobic N-terminal domain (226 residues); and 12 residues of the first epidermal growth factor (EGF)-like repeat (COSdel.238 cells) were found to function normally with respect to TM transport to the cell surface and thrombin-dependent protein C activation. However, in contrast to wild-type TM, as visually studied by immunofluorescence and immunogold electron microscopy, the COSdel.238 cells did not constitutively internalize anti-TM-TM or thrombin-TM complexes. To identify the region responsible for mediating the endocytic process, deletant forms of TM lacking either the lectin-like region (residues 2-155) or the hydrophobic region of the N-terminal domain (residues 161-202) were expressed in COS cells (COSdel.2-155 and COSdel.161-202, respectively). Protein C cofactor activity was maintained in both cells. Although the COSdel.161-202 cells behaved similarly to wild-type TM-transfected cells, visual studies showed a lack of constitutive internalization of thrombin-TM or anti-TM-TM complexes in the COSdel.2-155 cells. We conclude that the lectin-like domain of human TM serves to regulate cell surface expression of TM via the endocytic route and therefore may also play a major physiologic role in controlling intracellular and extracellular accumulation of thrombin in a variety of biologic systems. |
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Authors:
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E M Conway; S Pollefeyt; D Collen; M Steiner-Mosonyi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Blood Volume: 89 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 1997 Jan |
Date Detail:
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Created Date: 1997-02-24 Completed Date: 1997-02-24 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 652-61 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, University of Toronto, Ontario, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals COS Cells Gene Transfer Techniques Humans Molecular Sequence Data Peptide Mapping Structure-Activity Relationship Thrombomodulin / chemistry*, physiology |
| Chemical | |
Reg. No./Substance:
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0/Thrombomodulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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