title: Regulation of Src-family protein tyrosine kinase transcription during lymphocyte ontogeny.
abstract: The distribution and quantity of cellular signaling elements influence response patterns to a variety of stimuli. As protein tyrosine phosphorylation is a requisite event induced by a majority of surface receptors, and protein tyrosine kinases of the src-family (src-PTKs) act as proximal transducers for many hematopoietic receptors, we have designed a quantitative RT-PCR assay to measure src-family PTK expression during critical stages of lymphocyte ontogeny. With this assay we demonstrate that the distal promoter element regulating expression of lck, a src-PTK essential for T-cell development and activation, is similarly regulated during ontogeny of T and B cells. However, lck transcript abundance is drastically reduced in B lineage cells, suggesting that transcriptional elements influencing lck promoter activity are modulated in these cells. Moreover, although transcripts encoding the src-PTK fyn accumulate at 0.1% of lck mRNA levels in thymocytes, diminished activity of the lck distal promoter in the B-cell background brings lck and fyn transcript levels to near equivalence in this population. Importantly, transcripts arising from the lck distal promoter element and the fyn locus are similarly upregulated during developmental transitions associated with antigen-receptor expression in both B and T cells. These findings suggest that although the magnitude of lck and fyn expression is differentially regulated in B and T cells, expression at these loci is similarly developmentally programmed during ontogeny of both lymphocyte lineages.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201-1559, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Longo
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: R S
authors.initials: RS
authors.lastname: Wildin
authors.forename: K M
authors.initials: KM
authors.lastname: Abraham
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005333:Fetus / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000592:standards; D016133:Polymerase Chain Reaction / Q000379:methods / Q000592:standards; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012015:Reference Standards; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D019061:src-Family Kinases / Q000235:genetics*
chemical_list: D017931:DNA Primers; D020648:Peptide Elongation Factor 1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases