PMID- 19734904
OWN - NLM
STAT- MEDLINE
DCOM- 20091009
LR  - 20211020
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 10
IP  - 10
DP  - 2009 Oct
TI  - Ras orchestrates exit from the cell cycle and light-chain recombination during 
      early B cell development.
PG  - 1110-7
LID - 10.1038/ni.1785 [doi]
AB  - Signals through the pre-B cell antigen receptor (pre-BCR) and interleukin 7 
      receptor (IL-7R) coordinate pre-B cell population expansion with subsequent 
      recombination of the locus encoding immunoglobulin kappa-chain (Igk). Although 
      many 'downstream' effectors of each receptor are known, how they integrate to 
      mediate development has remained unclear. Here we report that pre-BCR-mediated 
      activation of the Ras-MEK-Erk signaling pathway silenced transcription of Ccnd3 
      (encoding cyclin D3) and coordinated exit from the cell cycle with induction of 
      the transcription factor E2A and the initiation of Igk recombination. 
      IL-7R-mediated activation of the transcription factor STAT5 opposed this pathway 
      by promoting Ccnd3 expression and concomitantly inhibiting Igk transcription by 
      binding to the Igk intronic enhancer and preventing E2A recruitment. Our data 
      show how pre-BCR signaling poises pre-B cells to undergo differentiation after 
      escape from IL-7R signaling.
FAU - Mandal, Malay
AU  - Mandal M
AD  - Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, 
      Illinois, USA.
FAU - Powers, Sarah E
AU  - Powers SE
FAU - Ochiai, Kyoko
AU  - Ochiai K
FAU - Georgopoulos, Katia
AU  - Georgopoulos K
FAU - Kee, Barbara L
AU  - Kee BL
FAU - Singh, Harinder
AU  - Singh H
FAU - Clark, Marcus R
AU  - Clark MR
LA  - eng
GR  - R01 GM052736/GM/NIGMS NIH HHS/United States
GR  - R01 GM067772-04/GM/NIGMS NIH HHS/United States
GR  - R01 GM052736-10/GM/NIGMS NIH HHS/United States
GR  - R01 GM052736-11/GM/NIGMS NIH HHS/United States
GR  - R01 GM067772-04S1/GM/NIGMS NIH HHS/United States
GR  - R01 GM088847/GM/NIGMS NIH HHS/United States
GR  - R01 GM088847-01A2/GM/NIGMS NIH HHS/United States
GR  - R01 GM067772/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20090906
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Ccnd3 protein, mouse)
RN  - 0 (Cyclin D3)
RN  - 0 (Cyclins)
RN  - 0 (Immunoglobulin Light Chains)
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Tcf3 protein, mouse)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/*cytology/immunology
MH  - Basic Helix-Loop-Helix Transcription Factors/immunology/metabolism
MH  - Cell Cycle/genetics/*immunology
MH  - Cell Differentiation/*immunology
MH  - Cyclin D3
MH  - Cyclins/immunology/metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Extracellular Signal-Regulated MAP Kinases/immunology
MH  - Flow Cytometry
MH  - Gene Expression Regulation/immunology
MH  - Gene Silencing/immunology
MH  - Immunoblotting
MH  - Immunoglobulin Light Chains/*genetics
MH  - MAP Kinase Kinase Kinases/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Oligonucleotide Array Sequence Analysis
MH  - Receptors, Interleukin-7/immunology/metabolism
MH  - Recombination, Genetic
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - STAT5 Transcription Factor/immunology/metabolism
MH  - Signal Transduction/*immunology
MH  - ras Proteins/genetics/*immunology/metabolism
PMC - PMC3057509
MID - NIHMS249116
EDAT- 2009/09/08 06:00
MHDA- 2009/10/10 06:00
PMCR- 2011/03/15
CRDT- 2009/09/08 06:00
PHST- 2009/06/12 00:00 [received]
PHST- 2009/07/27 00:00 [accepted]
PHST- 2009/09/08 06:00 [entrez]
PHST- 2009/09/08 06:00 [pubmed]
PHST- 2009/10/10 06:00 [medline]
PHST- 2011/03/15 00:00 [pmc-release]
AID - ni.1785 [pii]
AID - 10.1038/ni.1785 [doi]
PST - ppublish
SO  - Nat Immunol. 2009 Oct;10(10):1110-7. doi: 10.1038/ni.1785. Epub 2009 Sep 6.