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rdf:type |
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lifeskim:mentions |
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0061928,
umls-concept:C0168424,
umls-concept:C0345904,
umls-concept:C0392337,
umls-concept:C0919437,
umls-concept:C1167622,
umls-concept:C1537044,
umls-concept:C1546857,
umls-concept:C1553877,
umls-concept:C1608885,
umls-concept:C1880274
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pubmed:issue |
21
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pubmed:dateCreated |
2007-5-23
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pubmed:abstractText |
The three deleted in liver cancer genes (DLC1-3) encode Rho-GTPase-activating proteins (RhoGAPs) whose expression is frequently down-regulated or silenced in a variety of human malignancies. The RhoGAP activity is required for full DLC-dependent tumor suppressor activity. Here we report that DLC1 and DLC3 bind to human tensin1 and its chicken homolog. The binding has been mapped to the tensin Src homology 2 (SH2) and phosphotyrosine binding (PTB) domains at the C terminus of tensin proteins. Distinct DLC1 sequences are required for SH2 and PTB binding. DCL binding to both domains is constitutive under basal conditions. The SH2 binding depends on a tyrosine in DCL1 (Y442) but is phosphotyrosine-independent, a highly unusual feature for SH2 binding. DLC1 competed with the binding of other proteins to the tensin C terminus, including beta 3-integrin binding to the PTB domain. Point mutation of a critical tyrosine residue (Y442F) in DLC1 rendered the protein deficient for binding the tensin SH2 domain and binding full-length tensin. The Y442F protein was diffusely cytoplasmic, in contrast to the localization of wild-type DLC1 to focal adhesions, but it retained the ability to reduce the intracellular levels of Rho-GTP. The Y442F mutant displayed markedly reduced biological activity, as did a mutant that was RhoGAP-deficient. The results suggest that DLC1 is a multifunctional protein whose biological activity depends on cooperation between its tensin binding and RhoGAP activities, although neither activity depends on the other.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-10783236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-11823424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-12495434,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-12531887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-12606711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-14647417,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-14674764,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-14694107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-14723705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-14999150,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-14999155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-15273989,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-15286780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-15506980,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-15567406,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-15680235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-15892119,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-16024604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-16204057,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-16489177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-16493427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-16533763,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-16774933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-16862168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-16951145,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-17016643,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-17190795,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17517630-9605766
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
104
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9012-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17517630-Animals,
pubmed-meshheading:17517630-Cell Line,
pubmed-meshheading:17517630-GTPase-Activating Proteins,
pubmed-meshheading:17517630-Humans,
pubmed-meshheading:17517630-Integrins,
pubmed-meshheading:17517630-Mice,
pubmed-meshheading:17517630-Microfilament Proteins,
pubmed-meshheading:17517630-Mutation,
pubmed-meshheading:17517630-Oncogene Proteins,
pubmed-meshheading:17517630-Phosphotyrosine,
pubmed-meshheading:17517630-Protein Binding,
pubmed-meshheading:17517630-Tumor Suppressor Proteins,
pubmed-meshheading:17517630-Tyrosine,
pubmed-meshheading:17517630-src Homology Domains
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pubmed:year |
2007
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pubmed:articleTitle |
Oncogenic inhibition by a deleted in liver cancer gene requires cooperation between tensin binding and Rho-specific GTPase-activating protein activities.
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pubmed:affiliation |
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
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