DOI: 10.1101/gad.8.6.688. An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement.

An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement.

10.1101/gad.8.6.688

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

Lymphoid cells transformed by Abelson murine leukemia virus have provided one of the classic models for study of early B-cell development and immunoglobulin rearrangement. Most of these cells have rearranged their heavy-chain locus but not their light chain genes, suggesting that an active v-abl protein interferes with this differentiation step. To test this hypothesis, light-chain gene structure was examined in pre-B cells transformed by temperature-sensitive mutants of the Abelson virus and in derivatives that survive at the nonpermissive temperature because they express a human BCL-2 gene. Our studies reveal that inactivation of the v-abl protein tyrosine kinase triggers high-frequency rearrangement of kappa and lambda light-chain genes. These events are accompanied by marked increases in the expression of RAG-1 and RAG-2 RNAs. These increases occur in the absence of protein synthesis but are dependent on inactivation of the v-abl protein tyrosine kinase. As documented in the accompanying paper (Klug et al., this issue), an active v-abl protein also suppresses the activity of NF-kappa B/rel and expression controlled by the kappa intron enhancer. Together these data demonstrate that the v-abl protein specifically interferes with light-chain gene rearrangement by suppressing at least two pathways essential for this stage of B-cell differentiation and suggest that tyrosine phosphorylation is important in regulating RAG gene expression.

Bibliography

Chen, Y. Y., Wang, L. C., Huang, M. S., & Rosenberg, N. (1994). An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement. Genes & Development, 8(6), 688â697.

Authors 4

Y Y Chen (first)
L C Wang (additional)
M S Huang (additional)
N Rosenberg (additional)

References 52 Referenced 108

{'key': '2021111418133512000_8.6.688.1', 'first-page': '386', 'article-title': 'Multiple immunoglobulin heavy-chain gene transcripts in Abelson murine leukemia virus-transformed pre-B cell lines.', 'volume': '2', 'year': '1982', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Multiple immunoglobulin heavy-chain gene transcripts in Abelson murine leukemia virus-transformed pre-B cell lines. (1982)
10.1002/j.1460-2075.1984.tb01955.x / EMBO J. / Ordered rearrangements of immunoglobulin heavy chain variable region segments. (1984)
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10.1016/0092-8674(87)90362-X
10.1002/j.1460-2075.1993.tb05722.x / EMBO J. / B cell development in mice that lack one or both immunoglobulin κ light chain genes. (1993)
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10.1016/0092-8674(91)90546-B
{'key': '2021111418133512000_8.6.688.12', 'first-page': '571', 'article-title': 'Influence of CpG methylation and target spacing on V(D)J recombination in a transgenic substrate.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Influence of CpG methylation and target spacing on V(D)J recombination in a transgenic substrate. (1993)
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10.1016/0092-8674(87)90615-5
10.1038/348334a0
10.1101/gad.7.10.2016
Klug, C.A., Gerety, S.J. Chen, Y.Y. Rice, N.R. Rosenberg, N. and Singh. H. 1994. The v-abl tyrosine kinase negatively regulates NF-κB/rel and blocks κ gene transcription in pre-B lymphocytes. Genes & Dev. (this issue). (10.1101/gad.8.6.678)
10.1016/0092-8674(89)90833-7
10.1126/science.3109035
10.4049/jimmunol.144.5.1983 / J. Immunol. / The temporal order of appearance of transcripts from unrearranged and rearranged Ig genes in murine fetal liver. (1990)
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10.4049/jimmunol.144.9.3602 / J. Immunol. / Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. (1990)
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{'key': '2021111418133512000_8.6.688.35', 'first-page': '6223', 'article-title': 'A V(D)J recombinase-inducible B-cell line: Role of transcriptional enhancer elements in directing V(D)J recombination.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / A V(D)J recombinase-inducible B-cell line: Role of transcriptional enhancer elements in directing V(D)J recombination. (1993)
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{'key': '2021111418133512000_8.6.688.37', 'first-page': '5216', 'article-title': 'Novel B-cell precursors blocked at the stage of DJH recombination.', 'volume': '8', 'year': '1988', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Novel B-cell precursors blocked at the stage of DJH recombination. (1988)
10.1002/j.1460-2075.1986.tb04476.x / EMBO J. / VHDJH formation and DJH replacement during pre-B differentiation: Nonrandom usage of gene segments. (1986)
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{'key': '2021111418133512000_8.6.688.47', 'first-page': '5679', 'article-title': 'Stimulation of κ light-chain gene rearrangement by the immunoglobulin µ heavy chain in a pre-B-cell line.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Stimulation of κ light-chain gene rearrangement by the immunoglobulin µ heavy chain in a pre-B-cell line. (1993)
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Dates

Type	When
Created	18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited	2 years, 3 months ago (May 12, 2023, 2:25 a.m.)
Indexed	2 months ago (June 26, 2025, 2:25 p.m.)
Issued	31 years, 5 months ago (March 15, 1994)
Published	31 years, 5 months ago (March 15, 1994)
Published Online	31 years, 5 months ago (March 15, 1994)
Published Print	31 years, 5 months ago (March 15, 1994)

Funders 0

None

BibTeX

@article{Chen_1994, title={An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement.}, volume={8}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.8.6.688}, DOI={10.1101/gad.8.6.688}, number={6}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Chen, Y Y and Wang, L C and Huang, M S and Rosenberg, N}, year={1994}, month=mar, pages={688–697} }

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