Overexpression of src family gene for tyrosine-kinase p59fyn in CD4-CD8- T cells of mice with a lymphoproliferative disorder.
Overexpression of a src family gene, lck, has been associated with differentiation of the murine thymic lymphoma line LSTRA. Recent findings by several groups strongly suggest a functional role for the gene product p56lck protein-tyrosine kinase (PTK) in the activation of normal T cells. A single recessive gene, lpr or gld, induces a lymphoproliferative disorder concomitant with autoimmune disease in mice. In this study, a 10-fold elevated activity of PTK encoded by fyn, another src family gene, was demonstrated in CD4-CD8- T cells in mutant mice. The increased PTK activity was consistent with overexpression of fyn mRNA. The elevated fyn mRNA expression appeared to be a characteristic of CD4-CD8- T cells, since it was not observed in normal T cells at any stage of differentiation. The fact that fyn mRNA expression was markedly induced in normal T cells by mitogenic stimulation with anti-T3 epsilon antiserum supports the possibility that p59fyn PTK is a signal-generating molecule in T cells. Thus, our findings provide insight into the physiological role for a src gene family kinase in T-cell development and contribute to a better understanding of the molecular mechanisms of disease-inducing recessive genes.
Katagiri
T
T
Department of Immunology, University of Tokyo, Japan.
Urakawa
K
K
Yamanashi
Y
Y
Semba
K
K
Takahashi
T
T
Toyoshima
K
K
Yamamoto
T
T
Kano
K
K
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D015704:CD4 Antigens / Q000235:genetics*; D016827:CD8 Antigens; D002454:Cell Differentiation; D005260:Female; D015870:Gene Expression; D015151:Immunoblotting; D008198:Lymph Nodes / Q000201:enzymology / Q000276:immunology; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D005810:Multigene Family; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051076:Proto-Oncogene Proteins c-fyn; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D013950:Thymus Gland / Q000201:enzymology / Q000276:immunology; D014158:Transcription, Genetic
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn