title: Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling.
abstract: The specificity of the various STAT SH2 domains for different tyrosine-containing peptides enables cytokines to activate different signaling pathways and to induce distinct patterns of gene expression. We show that STAT4 has a unique peptide specificity and binds to the peptide sequence pYLPSNID (where pY represents phosphotyrosine). This motif is found at tyrosine residue 800 in the beta2 subunit of the interleukin-12 receptor and is required for DNA binding and transcriptional activity of STAT4. Our data demonstrate that transfection of interleukin-12 receptor beta1 and beta2 subunits is sufficient for STAT4 activation but not for STAT1 or STAT3 activation.
authors.affiliation: Tularik, Inc., South San Francisco, California 94080, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Naeger
authors.forename: J
authors.initials: J
authors.lastname: McKinney
authors.forename: A
authors.initials: A
authors.lastname: Salvekar
authors.forename: T
authors.initials: T
authors.lastname: Hoey
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D015534:Trans-Activators; D014443:Tyrosine