BASH-novel PKC-Raf-1 pathway of pre-BCR signaling induces kappa gene rearrangement.
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 kappaL-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 PKCeta, PKCepsilon, or Raf-1, but not Ras, induced the kappa gene rearrangement and expression in the pre-B-cell line. Tamoxifen-mediated BASH reconstitution resulted in the translocation of PKCeta to the plasma membrane and kappa 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.
Yamamoto
Mutsumi
M
Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Yamazaki 2669, Noda, Chiba 278-0022, Japan.
Hayashi
Katsuhiko
K
Nojima
Takuya
T
Matsuzaki
Yumi
Y
Kawano
Yohei
Y
Karasuyama
Hajime
H
Goitsuka
Ryo
R
Kitamura
Daisuke
D
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D015448:Leukemia, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D011289:Preleukemia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D004273:DNA, Neoplasm; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins