Inducible binding to the c-fos serum response element during T cell activation is regulated by a phosphotyrosine-containing protein.
The proto-oncogene c-fos is an immediate-early gene, and one of the first genes transcribed after stimulation of most cells with a variety of ligands. Fos expression may be a pivotal event in converting ligand-receptor interactions at the membrane into functional modulation of cell phenotype. The serum response element (SRE) in the c-fos regulatory region participates in induction of transcription by various growth factors and by phorbol esters and subsequent squelching of transcription. We show that an inducible protein complex (Band A) binds to SRE DNA within 10 min after mitogenic stimulation of human PBL-T, and becomes nondetectable by 60 min. Band A contains the serum response factor plus additional factor(s). A protein that is phosphorylated on a tyrosine residue in resting PBL-T suppresses binding of a component of Band A to the SRE motif. Upon stimulation of the cells, this protein no longer prevents binding of DNA by Band A, and suppression of binding is restored within 30 min. The phosphorylated tyrosine residue itself is important for the protein-protein interaction.
Benson
B A
BA
Department of Pharmacology and Toxicology, University of Kansas, Lawrence 66045.
Jonsen
M
M
Benedict
S H
SH
D001483:Base Sequence; D002478:Cells, Cultured; D002847:Chromatography, Agarose / Q000379:methods; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D016762:Genes, fos; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000502:physiology*; D019000:Phosphotyrosine; D000090063:Proto-Oncogene Mas; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D019000:Phosphotyrosine; D014443:Tyrosine