SEARCH:   Advanced

Blood, 15 February 2008, Vol. 111, No. 4, pp. 2310-2320. Prepublished online as a Blood First Edition Paper on December 10, 2007; DOI 10.1182/blood-2007-05-090985. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-05-090985v1 111/4/2310    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Tauzin, S. Articles by Hoessli, D. C. PubMed PubMed Citation Articles by Tauzin, S. Articles by Hoessli, D. C. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine kinase in human B-NHL rafts Sebastien Tauzin1, Heidrun Ding1, Karim Khatib1, Ishtiaq Ahmad2, Dimitri Burdevet1, Gerhild van Echten-Deckert3, Jonathan A. Lindquist4, Burkhart Schraven4, Nasir-ud- Din2, Bettina Borisch1,5, and Daniel C. Hoessli1 1 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; 2 Institute of Molecular Sciences and Bioinformatics, Lahore, Pakistan; 3 Kekulé-Institut für Organische Chemie und Biochemie der Universität Bonn, Bonn, Germany; 4 Institute of Immunology, Otto-von-Guericke University, Magdeburg, Germany; and 5 Institute of Social and Preventive Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland B-non-Hodgkin lymphomas (B-NHLs) use a raft-associated signalosome made of the constitutively active Lyn kinase, the tyrosine phosphorylated Cbp/PAG adaptor, and tyrosine phosphorylated STAT3 transcription factor. No such "signalosome" is found in rafts of ALK+ T lymphoma and Hodgkin-derived cell lines, despite similar Cbp/PAG, Lyn, and STAT3 expression and similar amounts of raft sphingolipids. Stable association of the signalosome with B-NHL rafts requires (1) a Lyn kinase (auto)phosphorylated in its regulatory and active site tyrosines, (2) a Cbp/PAG adaptor phosphorylated at tyrosine 317 and bound to Lyn SH2 via phosphotyrosine 299 and neighboring residues, and (3) a tyrosine phosphorylated STAT3 linked via SH2 to the regulatory, C-terminal tyrosine of Lyn. No Csk appears to be part of this B-NHL signalosome. An oncogenic role for Lyn was shown after exposure of B-NHL lines to Lyn inhibitors that prevented Lyn and Cbp/PAG phosphorylation, dissociated the signalosome from rafts, and eventually induced death. Cell death followed decreases in Lyn or Cbp/PAG expression levels in one mantle cell lymphoma line, but not in a Hodgkin-derived one. The Lyn-Cbp/PAG signalosome appears to control proliferation and survival in most B-NHLs and constitutes a therapeutic target in B-NHL cells that exhibit oncogenic "addiction" to the Lyn kinase. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020