Protein tyrosine kinase p56lck controls allelic exclusion of T-cell receptor β-chain genes
- 1 October 1993
- journal article
- Published by Springer Nature in Nature
- Vol. 365 (6446) , 552-554
- https://doi.org/10.1038/365552a0
Abstract
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.Keywords
This publication has 23 references indexed in Scilit:
- Restoration of T Cell Development in RAG-2-Deficient Mice by Functional TCR TransgenesScience, 1993
- Mutations in T-cell antigen receptor genes α and β block thymocyte development at different stagesNature, 1992
- Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptorCell, 1992
- RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangementCell, 1992
- RAG-1-deficient mice have no mature B and T lymphocytesCell, 1992
- Developmental regulation of lck gene expression in T lymphocytes.The Journal of Experimental Medicine, 1991
- The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lckCell, 1988
- Structure and expression of Ick transcripts in human lymphoid cellsJournal of Cellular Biochemistry, 1988
- The Developmental Biology of T LymphocytesAnnual Review of Immunology, 1988
- Allelic Exclusion in Transgenic Mice That Express the Membrane form of Immunoglobulin μScience, 1987