INHIBITION OF T-CELL RECEPTOR BETA-CHAIN GENE REARRANGEMENT BY OVEREXPRESSION OF THE NONRECEPTOR PROTEIN TYROSINE KINASE-P56LCK

被引:184
作者
ANDERSON, SJ
ABRAHAM, KM
NAKAYAMA, T
SINGER, A
PERLMUTTER, RM
机构
[1] UNIV WASHINGTON,DEPT IMMUNOL,SEATTLE,WA 98195
[2] UNIV WASHINGTON,HOWARD HUGHES MED INST,SEATTLE,WA 98195
[3] UNIV WASHINGTON,DEPT BIOCHEM & MED,SEATTLE,WA 98195
[4] NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892
关键词
GERMLINE TRANSCRIPTION; LCK TRANSGENIC MICE; V-BETA REARRANGEMENT;
D O I
10.1002/j.1460-2075.1992.tb05594.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Vbeta-Dbeta 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.
引用
收藏
页码:4877 / 4886
页数:10
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