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Characterization of interleukin-7-induced changes in tyrosine phosphorylation and c-myc gene expression in normal human T cells.
- Source :
-
Experimental hematology [Exp Hematol] 1993 Dec; Vol. 21 (13), pp. 1648-56. - Publication Year :
- 1993
-
Abstract
- Interleukin-7 (IL-7) is a growth factor involved in regulating lymphopoiesis. We have chosen to study the signal transduction pathway of IL-7 in normal human peripheral blood T lymphocytes. Two early events that occur as a consequence of specific ligand-receptor interaction were examined: activation of protein tyrosine kinases and induction of primary response gene expression. Following treatment of human peripheral blood T cells with IL-7, four cellular proteins with relative molecular weights of 95- (doublet), 105-, and 130-kd were rapidly tyrosine phosphorylated as detected by immunoblotting with an antiphosphotyrosine monoclonal antibody (MAB). The 105-kd tyrosine-phosphorylated protein was membrane-associated after IL-7 stimulation. Treatment of human peripheral blood T cells with IL-7 enhanced expression of the primary response gene c-myc approximately three-fold, as detected by Northern blotting, in the presence or absence of protein synthesis. The rate of c-myc gene transcription increased in the presence of IL-7 and could account for the observed elevation of c-myc RNA levels. In addition, IL-7 treatment induced a slight increase in c-myc message stability. Experiments performed with the protein tyrosine kinase inhibitor genistein and the serine-threonine kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7) demonstrated that these kinases were required for IL-7 enhancement of c-myc expression. Treatment with tetradecanoyl phorbol acetate (TPA), a potent activator of protein kinase C (PKC), in combination with IL-7 induced a level of c-myc expression greater than that elicited by either factor alone, suggesting that TPA and IL-7 utilize cooperative signaling pathways to increase c-myc gene expression.
- Subjects :
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Blotting, Northern
Cell Division
Humans
Immunoblotting
Isoquinolines pharmacology
Molecular Weight
Phosphorylation
Phosphotyrosine
Piperazines pharmacology
Protein Kinase Inhibitors
Protein Kinases metabolism
Signal Transduction
T-Lymphocytes cytology
Tetradecanoylphorbol Acetate pharmacology
Transcription, Genetic
Tyrosine metabolism
Gene Expression drug effects
Genes, myc
Interleukin-7 pharmacology
Phosphoproteins metabolism
T-Lymphocytes metabolism
Tyrosine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0301-472X
- Volume :
- 21
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Experimental hematology
- Publication Type :
- Academic Journal
- Accession number :
- 7694866