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PMID: 1334460 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of T-cell receptor beta-chain gene rearrangement by overexpression of the non-receptor protein tyrosine kinase p56lck.

The EMBO journal ·Vol. 11 ·No. 13 ·1992-12-00 ·Pages 4877-86

Anderson SJ, Abraham KM, Nakayama T, Singer A, Perlmutter RM

Abstract

The variable region genes of the T cell receptor (TCR) alpha and beta chains are assembled by somatic recombination of separate germline elements. During thymocyte development, gene rearrangements display both an ordered progression, with beta chain formation preceding alpha chain, and allelic exclusion, with each cell containing a single functional beta chain rearrangement. Although considerable evidence supports the view that the individual loci are regulated independently, signaling molecules that may participate in controlling TCR gene recombination remain unidentified. Here we report that the lymphocyte-specific protein tyrosine kinase p56lck, when overexpressed in developing thymocytes, provokes a reduction in V beta--D beta rearrangement while permitting normal juxtaposition of other TCR gene segments. Our data support a model in which p56lck activity impinges upon a signaling process that ordinarily permits allelic exclusion at the beta-chain locus.

MeSH Terms
Animals Base Sequence Blotting, Northern DNA, Single-Stranded Flow Cytometry Gene Rearrangement, beta-Chain T-Cell Antigen Receptor Immunoblotting Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Mice Mice, Transgenic Molecular Sequence Data Polymerase Chain Reaction Protein-Tyrosine Kinases/genetics,physiology Receptors, Antigen, T-Cell/genetics Thymus Gland/cytology Transcription, Genetic
Chemicals
DNA, Single-Stranded Receptors, Antigen, T-Cell Protein-Tyrosine Kinases Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Anderson S J
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Abraham K M
Nakayama T
Singer A
Perlmutter R M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-12-00
Pages
4877-86
Language
English
Region
England
NLM ID
8208664
PMCID
PMC556965
Subset
IM
Grants
NCI NIH HHS · CA45682 · United States
External Links
PubMed source PMC Full Text View journal details
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