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PMID: 14662906 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mimicry of pre-B cell receptor signaling by activation of the tyrosine kinase Blk.

The Journal of experimental medicine ·Vol. 198 ·No. 12 ·2003-12-15 ·Pages 1863-73

Tretter T, Ross AE, Dordai DI, Desiderio S

Abstract

During B lymphoid ontogeny, assembly of the pre-B cell receptor (BCR) is a principal developmental checkpoint at which several Src-related kinases may play redundant roles. Here the Src-related kinase Blk is shown to effect functions associated with the pre-BCR. B lymphoid expression of an active Blk mutant caused proliferation of B progenitor cells and enhanced responsiveness of these cells to interleukin 7. In mice lacking a functional pre-BCR, active Blk supported maturation beyond the pro-B cell stage, suppressed VH to DJH rearrangement, relieved selection for productive heavy chain rearrangement, and stimulated kappa rearrangement. These alterations were accompanied by tyrosine phosphorylation of immunoglobulin beta and Syk, as well as changes in gene expression consistent with developmental maturation. Thus, sustained activation of Blk induces responses normally associated with the pre-BCR.

MeSH Terms
Animals B-Lymphocytes/physiology Cells, Cultured Enzyme Activation Gene Rearrangement Genes, Immunoglobulin Immunoglobulin Heavy Chains/genetics Immunoglobulin kappa-Chains/genetics Interleukin-7/pharmacology Membrane Glycoproteins/physiology Mice Mice, Inbred C57BL Mice, Transgenic Pre-B Cell Receptors Receptors, Antigen, B-Cell Signal Transduction src-Family Kinases/metabolism
Chemicals
Immunoglobulin Heavy Chains Immunoglobulin kappa-Chains Interleukin-7 Membrane Glycoproteins Pre-B Cell Receptors Receptors, Antigen, B-Cell src-Family Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Tretter Theresa
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ross Ashley E
Dordai Dominic I
Desiderio Stephen
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20030729
Published
2003-12-15
Epub
2003-00-08
Pages
1863-73
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2194155
Subset
IM
Grants
NCI NIH HHS · P01 CA016519 · United States
NCI NIH HHS · CA16519 · United States
External Links
PubMed source DOI: 10.1084/jem.20030729 PMC Full Text View journal details
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