PMID- 15592516 OWN - NLM STAT- MEDLINE DCOM- 20050314 LR - 20131121 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 24 IP - 7 DP - 2005 Feb 10 TI - HTLV-I Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L). PG - 1262-71 AB - 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. FAU - Iwata, Satoshi AU - Iwata S AD - 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. FAU - Souta-Kuribara, Akiko AU - Souta-Kuribara A FAU - Yamakawa, Akio AU - Yamakawa A FAU - Sasaki, Takahiro AU - Sasaki T FAU - Shimizu, Takatsune AU - Shimizu T FAU - Hosono, Osamu AU - Hosono O FAU - Kawasaki, Hiroshi AU - Kawasaki H FAU - Tanaka, Hirotoshi AU - Tanaka H FAU - Dang, Nam H AU - Dang NH FAU - Watanabe, Toshiki AU - Watanabe T FAU - Arima, Naomichi AU - Arima N FAU - Morimoto, Chikao AU - Morimoto C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Gene Products, tax) RN - 0 (NEDD9 protein, human) RN - 0 (NF-kappa B) RN - 0 (Phosphoproteins) RN - J6K4F9V3BA (Cadmium Chloride) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Cadmium Chloride/pharmacology MH - Cell Line, Transformed MH - Cell Movement/genetics/physiology MH - Cytosol/chemistry MH - Gene Products, tax/analysis/*metabolism MH - Human T-lymphotropic virus 1/metabolism MH - Humans MH - Immunoprecipitation MH - Leukemia, T-Cell/*virology MH - Leukocytes, Mononuclear/chemistry/drug effects/physiology MH - NF-kappa B/physiology MH - Phosphoproteins/analysis/metabolism/*physiology MH - Phosphorylation MH - Transcriptional Activation/physiology MH - Two-Hybrid System Techniques MH - Up-Regulation EDAT- 2004/12/14 09:00 MHDA- 2005/03/15 09:00 CRDT- 2004/12/14 09:00 PHST- 2004/12/14 09:00 [pubmed] PHST- 2005/03/15 09:00 [medline] PHST- 2004/12/14 09:00 [entrez] AID - 1208261 [pii] AID - 10.1038/sj.onc.1208261 [doi] PST - ppublish SO - Oncogene. 2005 Feb 10;24(7):1262-71. doi: 10.1038/sj.onc.1208261.