| The cytosolic domain of protein-tyrosine kinase 7 (PTK7), generated from sequential cleavage by a disintegrin and metalloprotease 17 (ADAM17) and γ-secretase, enhances cell proliferation and migration in colon cancer cells. | |
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MedLine Citation:
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PMID: 22665490 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Protein-tyrosine kinase 7 (PTK7) is a member of the defective receptor protein-tyrosine kinases and is known to function as a regulator of planar cell polarity during development. Its expression is up-regulated in some cancers including colon carcinomas. A 100-kDa fragment of PTK7 was detected in the culture media from colon cancer cells and HEK293 cells. The shed fragment was named sPTK7-Ig1-7 because its molecular mass was very similar to that of the entire extracellular domain of PTK7 that contains immunoglobulin-like loops 1 to 7 (Ig1-7). The shedding of sPTK7-Ig1-7 was enhanced by treatment with phorbol 12-myristate 13-acetate. In addition to the sPTK7-Ig1-7 found in the culture medium, two C-terminal fragments of PTK7 were detected in the cell lysates: PTK7-CTF1, which includes a transmembrane segment and a cytoplasmic domain, and PTK7-CTF2, which lacks most of the transmembrane segment from PTK7-CTF1. Analysis of PTK7 processing in the presence of various protease inhibitors or after knockdown of potential proteases suggests that shedding of PTK7 into sPTK7-Ig1-7 and PTK7-CTF1 is catalyzed by ADAM17, and further cleavage of PTK7-CTF1 into PTK7-CTF2 is mediated by the γ-secretase complex. PTK7-CTF2 localizes to the nucleus and enhances proliferation, migration, and anchorage-independent colony formation. Our findings demonstrate a novel role for PTK7 in the tumorigenesis via generation of PTK7-CTF2 by sequential cleavage of ADAM17 and γ-secretase. |
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Authors:
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Hye-Won Na; Won-Sik Shin; Andreas Ludwig; Seung-Taek Lee |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-06-04 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-07-23 Completed Date: 2012-10-18 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 25001-9 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ADAM Proteins
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genetics,
metabolism* Amyloid Precursor Protein Secretases / genetics, metabolism* Cell Adhesion Molecules / genetics, metabolism* Cell Line, Tumor Cell Movement* Cell Proliferation* Cell Transformation, Neoplastic Colonic Neoplasms / genetics, metabolism* HEK293 Cells Humans Neoplasm Proteins / genetics, metabolism* Protein Structure, Secondary Protein Structure, Tertiary Proteolysis* Receptor Protein-Tyrosine Kinases / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Cell Adhesion Molecules; 0/Neoplasm Proteins; EC 2.7.1.-/PTK7 protein, human; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 3.4.-/Amyloid Precursor Protein Secretases; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/tumor necrosis factor-alpha convertase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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