Identification of a putative regulator of early T cell activation genes.
Molecules involved in the antigen receptor-dependent regulation of early T cell activation genes were investigated with the use of functional sequences of the T cell activation-specific enhancer of interleukin-2 (IL-2). One of these sequences forms a protein complex, NFAT-1, specifically with nuclear extracts of activated T cells. This complex appeared 10 to 25 minutes before the activation of the IL-2 gene. Studies with inhibitors of protein synthesis indicated that the time of synthesis of the activator of the IL-2 gene in Jurkat T cells corresponds to the time of appearance of NFAT-1. NFAT-1, or a very similar protein, bound functional sequences of the long terminal repeat (LTR) of the human immunodeficiency virus type 1; the LTR of this virus is known to be stimulated during early T cell activation. The binding site for this complex activated a linked promoter after transfection into antigen receptor-activated T cells but not other cell types. These characteristics suggest that NFAT-1 transmits signals initiated at the T cell antigen receptor.
Shaw
J P
JP
Howard Hughes Medical Institute, Stanford University, CA 94305.
Utz
P J
PJ
Durand
D B
DB
Toole
J J
JJ
Emmel
E A
EA
Crabtree
G R
GR
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D006678:HIV / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D009687:Nuclear Proteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors