Document Detail

Cytoplasmic retention of protein tyrosine kinase 6 promotes growth of prostate tumor cells.
MedLine Citation:
PMID:  20953141     Owner:  NLM     Status:  MEDLINE    
Protein tyrosine kinase 6 (PTK6) is an intracellular tyrosine kinase that is nuclear in epithelial cells of the normal prostate, but cytoplasmic in prostate tumors and in the PC3 prostate tumor cell line. The impact of altered PTK6 intracellular localization in prostate tumor cells has not been extensively explored. Knockdown of endogenous cytoplasmic PTK6 resulted in decreased PC3 cell proliferation and colony formation, suggesting that cytoplasmic PTK6 stimulates oncogenic pathways. In contrast, reintroduction of PTK6 into nuclei of PC3 cells had a negative effect on growth. Enhanced tyrosine phosphorylation of the PTK6 substrate Sam68 was detected in cells expressing nuclear-targeted PTK6. We found that mechanisms regulating nuclear localization of PTK6 are intact in PC3 cells. Transiently overexpressed PTK6 readily enters the nucleus. Ectopic expression of ALT-PTK6, a catalytically inactive splice variant of PTK6, did not affect localization of endogenous PTK6 in PC3 cells. Using leptomycin B, we confirmed that cytoplasmic localization of endogenous PTK6 is not due to Crm-1/exportin-1 mediated nuclear export. In addition, overexpression of the PTK6 nuclear substrate Sam68 is not sufficient to bring PTK6 into the nucleus. While exogenous PTK6 was readily detected in the nucleus when transiently expressed at high levels, low-level expression of inducible wild type PTK6 in stable cell lines resulted in its cytoplasmic retention. Our results suggest that retention of PTK6 in the cytoplasm of prostate cancer cells disrupts its ability to regulate nuclear substrates and leads to aberrant growth. In prostate cancer, restoring PTK6 nuclear localization may have therapeutic advantages.
Patrick M Brauer; Yu Zheng; Lin Wang; Angela L Tyner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-10-30
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  9     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-28     Completed Date:  2011-03-07     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4190-9     Citation Subset:  IM    
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MeSH Terms
Active Transport, Cell Nucleus / physiology
Adaptor Proteins, Signal Transducing / genetics,  metabolism
Cell Line, Tumor
Cell Nucleus / metabolism
Cytoplasm / enzymology*
DNA-Binding Proteins / genetics,  metabolism
Gene Knockdown Techniques
Karyopherins / metabolism
Neoplasm Proteins / genetics,  metabolism*
Nuclear Localization Signals
Prostatic Neoplasms / enzymology*,  pathology*
Protein-Tyrosine Kinases / genetics,  metabolism*
RNA-Binding Proteins / genetics,  metabolism
Receptors, Cytoplasmic and Nuclear / metabolism
Signal Transduction / physiology
Grant Support
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/DNA-Binding Proteins; 0/KHDRBS1 protein, human; 0/Karyopherins; 0/Neoplasm Proteins; 0/Nuclear Localization Signals; 0/RNA-Binding Proteins; 0/Receptors, Cytoplasmic and Nuclear; 0/exportin 1 protein; EC Kinases; EC protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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