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Co-ordination of the expression of the protein tyrosine kinase p56(lck) with the pre-T cell receptor during thymocyte development

Buckland, J., Pennington, D. J., Bruno, L. and Owen, Michael John 2000. Co-ordination of the expression of the protein tyrosine kinase p56(lck) with the pre-T cell receptor during thymocyte development. European Journal of Immunology 30 (1) , pp. 8-18. 10.1002/1521-4141(200001)30:1<8::AID-IMMU8>3.0.CO;2-8

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Abstract

The protein tyrosine kinase p56(lck) is essential for the regulation of early thymocyte development by transducing pre-T cell receptor (pre-TCR) mediated-signals. Here we have investigated the developmental timing of expression of p56(lck) in the thymus. We show that p56(lck) transcripts are detectable in each CD4(-)CD8(-) double-negative (DN) thymocyte subset defined by CD25 and CD44. The steady-state level of p56(lck) mRNA with these four DN subsets is similar, varying by less than 2-fold. However, p56(lck) protein levels are undetectable in DN subsets 1 and 2, but are at least 20-fold up-regulated between DN subsets 2 and 3. Analysis of independent transgenic mouse lines in which the proximal p56(lck) promoter was used to drive expression of a green fluorescent protein (GFP) reporter gene revealed a lack of correlation between GFP mRNA expression and transgene copy number and variable expression of GFP protein in different lines. Taken together these results show that the expression of the p56(lck) gene is developmentally regulated at the post-transcriptional level at the precise developmental stage at which its upstream receptor complex, the pre-TCR, is expressed. These results also have implications for the interpretation of the phenotype of transgenic mice which utilize the p56(lck) proximal promoter.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: John Wiley & Sons
ISSN: 0014-2980
Last Modified: 04 Jun 2017 08:37
URI: http://orca-mwe.cf.ac.uk/id/eprint/81194

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