| HTLV-I Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L). | |
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MedLine Citation:
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PMID: 15592516 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Crk-associated substrate lymphocyte type (Cas-L) is a docking protein that is heavily tyrosine phosphorylated by the engagement of beta1 integrins in T cells. In the present study, we attempted to evaluate the role of Cas-L in the pathophysiology of adult T-cell leukemia (ATL). Examination of peripheral blood mononuclear cells from ATL patients as well as ATL-derived T cell lines showed an elevation of Cas-L in these cells. We showed that tyrosine phosphorylation as well as expression of Cas-L was markedly elevated through the induction of human T-lymphotropic virus type I (HTLV-I) Tax in JPX-9 cells, with these cells showing marked motile behavior on the ligands for integrins. We next performed yeast two-hybrid screening of cDNA library from an HTLV-I-transformed T cell line, which resulted in the identification of Tax as a putative binding partner for Cas-L. Co-precipitation experiments revealed that the serine-rich region of Cas-L might serve as the binding site with the highest affinity for Tax. Co-localization study showed that Tax and Cas-L partly merged in the cytoplasm. Finally, we showed that exogenous Cas-L inhibited Tax-mediated transactivation of nuclear factor kappaB (NF-kappaB), while Tax-independent activation of NF-kappaB remained intact, hence indicating that Cas-L might specifically regulate Tax-NF-kappaB pathway. |
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Authors:
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Satoshi Iwata; Akiko Souta-Kuribara; Akio Yamakawa; Takahiro Sasaki; Takatsune Shimizu; Osamu Hosono; Hiroshi Kawasaki; Hirotoshi Tanaka; Nam H Dang; Toshiki Watanabe; Naomichi Arima; Chikao Morimoto |
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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: Oncogene Volume: 24 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2005 Feb |
Date Detail:
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Created Date: 2005-02-11 Completed Date: 2005-03-14 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 1262-71 Citation Subset: IM |
Affiliation:
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Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing Cadmium Chloride / pharmacology Cell Line, Transformed Cell Movement / genetics, physiology Cytosol / chemistry Gene Products, tax / analysis, metabolism* Human T-lymphotropic virus 1 / metabolism Humans Immunoprecipitation Leukemia, T-Cell / virology* Leukocytes, Mononuclear / chemistry, drug effects, physiology NF-kappa B / physiology Phosphoproteins / analysis, metabolism, physiology* Phosphorylation Transcriptional Activation / physiology Two-Hybrid System Techniques Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Gene Products, tax; 0/NEDD9 protein, human; 0/NF-kappa B; 0/Phosphoproteins; 10108-64-2/Cadmium Chloride |
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