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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2703-2711. Prepublished online as a Blood First Edition Paper on June 22, 2006; DOI 10.1182/blood-2006-05-024968. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-024968v1 108/8/2703    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yamamoto, M. Articles by Kitamura, D. Search for Related Content PubMed PubMed Citation Articles by Yamamoto, M. Articles by Kitamura, D. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY BASH-novel PKC-Raf-1 pathway of pre-BCR signaling induces gene rearrangement Mutsumi Yamamoto, Katsuhiko Hayashi, Takuya Nojima, Yumi Matsuzaki, Yohei Kawano, Hajime Karasuyama, Ryo Goitsuka, and Daisuke Kitamura From the Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Chiba, Japan; Department of Physiology, Keio University School of Medicine, Tokyo, Japan; and Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. The pre-B-cell receptor (pre-BCR) is thought to signal transcriptional activation of the immunoglobulin light (L) chain gene locus, proceeding to its V-J rearrangement. The pre-BCR signaling pathway for this process is largely unknown but may involve the adaptor protein BASH (BLNK/SLP-65). Here we report that the pre-B leukemia cell lines established from affected BASH-deficient mice rearrange L-chain gene locus and down-regulate pre-BCR upon PMA treatment or BASH reconstitution. Analyses with specific inhibitors revealed that activation of novel PKC (nPKC) and MEK, but not Ras, is necessary for the rearrangement. Accordingly, retroviral transduction of active PKC, PKC, or Raf-1, but not Ras, induced the gene rearrangement and expression in the pre-B-cell line. Tamoxifen-mediated BASH reconstitution resulted in the translocation of PKC to the plasma membrane and chain expression. These data make evident that the Ras-independent BASH-nPKC-Raf-1 pathway of pre-BCR signaling induces the L-chain gene rearrangement and expression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Imamura, A. Oda, T. Katahira, K. Bundo, K. A. Pike, M. J. H. Ratcliffe, and D. Kitamura BLNK Binds Active H-Ras to Promote B Cell Receptor-mediated Capping and ERK Activation J. Biol. Chem., April 10, 2009; 284(15): 9804 - 9813. [Abstract] [Full Text] [PDF] J. Nakayama, M. Yamamoto, K. Hayashi, H. Satoh, K. Bundo, M. Kubo, R. Goitsuka, M. A. Farrar, and D. Kitamura BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3 Blood, February 12, 2009; 113(7): 1483 - 1492. [Abstract] [Full Text] [PDF] S. Alter-Wolf, B. B. Blomberg, and R. L. Riley Deviation of the B Cell Pathway in Senescent Mice Is Associated with Reduced Surrogate Light Chain Expression and Altered Immature B Cell Generation, Phenotype, and Light Chain Expression J. Immunol., January 1, 2009; 182(1): 138 - 147. [Abstract] [Full Text] [PDF] A. Oda, T. Ono, M. Yamamoto, R. Goitsuka, and D. Kitamura PKC{eta} directs induction of IRF-4 expression and Ig {kappa} gene rearrangement in pre-BCR signaling pathway Int. Immunol., November 1, 2008; 20(11): 1417 - 1426. [Abstract] [Full Text] [PDF]

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