Submitted May 22, 2006
Accepted June 11, 2006
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*
Research Institute for Biological Sciences, Tokyo University of Science
Department of Physiology, Keio University School of Medicine
Department of Immune Regulation, Tokyo Medical and Dental University Graduate School
* Corresponding author; email: kitamura{at}rs.noda.tus.ac.jp.
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.
