Protein tyrosine kinase p56lck controls allelic exclusion of T-cell receptor beta-chain genes.
During T-cell development, site-specific DNA rearrangements mediating assembly of beta- and alpha-chain genes of the T-cell receptor (TCR) are developmentally ordered. In particular, assembly and expression of a complete beta-chain gene blocks further rearrangements at the beta-locus (a process referred to as allelic exclusion) and drives the generation and expansion of CD4+8+ cells. Although the mechanism used by TCR beta chains to deliver such signals is unknown, studies in transgenic animals have suggested that the lymphocyte-specific protein tyrosine kinase p56lck may impinge on a similar signalling pathway. The hypothesis that TCR beta chains deliver intracellular signals via p56lck makes an explicit prediction: that interference with p56lck function will mitigate the effects of a simultaneously expressed TCR beta chain. Here we confirm this prediction through examination of allelic exclusion in mice expressing both a functional TCR beta chain transgene and a catalytically inactive form of p56lck.
Anderson
S J
SJ
Howard Hughes Medical Institute, University of Washington School of Medicine, SL-15, Seattle 98195.
Levin
S D
SD
Perlmutter
R M
RM
D000483:Alleles; D000818:Animals; D015704:CD4 Antigens; D016827:CD8 Antigens; D005260:Female; D005434:Flow Cytometry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006411:Hematopoiesis, Extramedullary; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology
D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)