PMID- 8617239
OWN - NLM
STAT- MEDLINE
DCOM- 19960610
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 15
IP  - 8
DP  - 1996 Apr 15
TI  - The interleukin-7 receptor alpha chain transmits distinct signals for 
      proliferation and differentiation during B lymphopoiesis.
PG  - 1924-32
AB  - The interleukin 7 receptor (IL7R), which contains a unique alpha chain and a 
      gamma chain shared by other cytokine receptors, is indispensable for normal 
      lymphocyte development. The basis for this role is poorly understood. Here we 
      show that the IL7R alpha chain not only causes progenitors to proliferate, but 
      also has a distinct activity in inducing differentiation. First, we identify a 
      single cytoplasmic tyrosine residue in the IL7R alpha chain that is essential for 
      cell cycle entry and proliferation dependent on phosphatidylinositol 3-kinase. We 
      use a mutant alpha chain in which this residue has been altered to reconstitute B 
      lymphopoiesis by retrovirus-mediated gene transfer in cultures of bone marrow 
      from mice deficient in IL7R alpha chain. The mutation abrogates the proliferation 
      of B-lymphocyte progenitors, but reveals a novel function of the alpha chain in 
      promoting immunoglobulin heavy chain gene rearrangement leading to B-cell 
      differentiation. This function is lost (but proliferation sustained) when the 
      cytoplasmic domain of IL7R alpha is replaced by corresponding sequences from the 
      IL2R, despite the similarity on their signalling mechanisms. Thus, the signals 
      which mediate a differentiative function of the IL7R in B lymphopoiesis are 
      specific and distinct from those causing proliferation.
FAU - Corcoran, A E
AU  - Corcoran AE
AD  - Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK.
FAU - Smart, F M
AU  - Smart FM
FAU - Cowling, R J
AU  - Cowling RJ
FAU - Crompton, T
AU  - Crompton T
FAU - Owen, M J
AU  - Owen MJ
FAU - Venkitaraman, A R
AU  - Venkitaraman AR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Antigens, CD)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
SB  - IM
MH  - Animals
MH  - Antigens, CD/chemistry/genetics/*physiology
MH  - B-Lymphocytes/cytology/*immunology
MH  - Cell Differentiation
MH  - Cell Division
MH  - Gene Transfer Techniques
MH  - Genetic Complementation Test
MH  - Hematopoiesis
MH  - Hematopoietic Stem Cells/cytology/immunology
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Structure
MH  - Mutation
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphotransferases (Alcohol Group Acceptor)/metabolism
MH  - Protein Conformation
MH  - Receptors, Interleukin/chemistry/genetics/*physiology
MH  - Receptors, Interleukin-7
MH  - Recombinant Fusion Proteins/chemistry/genetics/physiology
MH  - Retroviridae/genetics
MH  - Signal Transduction
MH  - Tyrosine/chemistry
PMC - PMC450111
EDAT- 1996/04/15 00:00
MHDA- 1996/04/15 00:01
PMCR- 1997/04/15
CRDT- 1996/04/15 00:00
PHST- 1996/04/15 00:00 [pubmed]
PHST- 1996/04/15 00:01 [medline]
PHST- 1996/04/15 00:00 [entrez]
PHST- 1997/04/15 00:00 [pmc-release]
PST - ppublish
SO  - EMBO J. 1996 Apr 15;15(8):1924-32.