Document Detail

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.
MedLine Citation:
PMID:  22665490     Owner:  NLM     Status:  MEDLINE    
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.
Hye-Won Na; Won-Sik Shin; Andreas Ludwig; Seung-Taek Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-04
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-23     Completed Date:  2012-10-18     Revised Date:  2013-07-23    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  25001-9     Citation Subset:  IM    
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
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MeSH Terms
ADAM Proteins / 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
Neoplasm Proteins / genetics,  metabolism*
Protein Structure, Secondary
Protein Structure, Tertiary
Receptor Protein-Tyrosine Kinases / genetics,  metabolism*
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/Neoplasm Proteins; EC 2.7.1.-/PTK7 protein, human; EC 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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