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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 (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 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tauzin, S. Articles by Hoessli, D. C. Search for Related Content PubMed PubMed Citation Articles by Tauzin, S. Articles by Hoessli, D. C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 16, 2007 Accepted November 24, 2007 Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine kinase in human B-NHL rafts Sebastien Tauzin, Heidrun Ding, Karim Khatib, Ishtiaq Ahmad, Dimitri Burdevet, Gerhild van Echten-Deckert, Jonathan A Lindquist, Burkhart Schraven, Nasir ud-Din, Bettina Borisch, and Daniel C. Hoessli* Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland Institute of Molecular Sciences and Bioinformatics, Lahore, Pakistan Kekule-Institut Organische Chemie und Biochemie, Universitat Bonn, Bonn, Germany Institute of Immunology, Otto-von-Guericke University, Magdeburg, Germany Institute of Social and Preventive Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland * Corresponding author; email: daniel.hoessli{at}medecine.unige.ch. B-non-Hodgkin lymphomas utilize 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. We suggest that stable association of the signalosome with B-NHL rafts requires (i) a Lyn kinase (auto)phosphorylated in its regulatory and active site tyrosines, (ii) a Cbp/PAG adaptor phosphorylated at tyrosine 317 and bound to Lyn SH2 via phosphotyrosine 299 and neighboring residues and (iii) a tyrosine phosphorylated STAT3 linked via SH2 to the regulatory, C-terminal tyrosine of Lyn. No Csk appears to be found in this B-NHL signalosome. An oncogenic role for Lyn was shown following 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? This article has been cited by other articles: C. Oneyama, T. Iino, K. Saito, K. Suzuki, A. Ogawa, and M. Okada Transforming Potential of Src Family Kinases Is Limited by the Cholesterol-Enriched Membrane Microdomain Mol. Cell. Biol., December 15, 2009; 29(24): 6462 - 6472. [Abstract] [Full Text] [PDF] L. Veracini, V. Simon, V. Richard, B. Schraven, V. Horejsi, S. Roche, and C. Benistant The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1 J. Cell Biol., August 11, 2008; 182(3): 603 - 614. [Abstract] [Full Text] [PDF]

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