Prolactin induces rapid p95/p70 tyrosine phosphorylation, and protein binding to GAS-like sites in the anx Icp35 and c-fos genes.
Several growth factors and cytokines have been proposed to act through signaling pathways related by their dependence on tyrosine phosphorylation of latent transcription factors, and their use of similar transcription factor binding sites. Related mechanisms have previously not been reported for prolactin, growth hormone, or any other glandular hormone. We have identified sequences in the annexin Icp35 gene that are related to regulatory sequences in mammary gland milk protein genes, and then used DNA binding assays to show that PRL induces transient expression of factors specific for these sequences. The sequences in question are partially related to the core homology of the interferon (IFN)gamma-activated sequence (GAS). Considering that the prolactin-regulated factors might be related to the p91 component of IFN gamma-activated factor, we used immunoassays to show that prolactin induced tyrosine phosphorylation of a protein that comigrated with immunoreactive relatives of p91, and that antibody to p91 specifically interfered with the prolactin-induced binding activity on the annexin Icp35 gene.
Sidis
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Y
Department of Physiology and Biophysics, University of Cincinnati College of Medicine, Ohio 45267.
Horseman
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D000818:Animals; D017302:Annexins / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D010856:Columbidae; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016762:Genes, fos; D015151:Immunoblotting; D008894:Milk Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology*; D012045:Regulatory Sequences, Nucleic Acid; D050794:STAT1 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism*
D017302:Annexins; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D014443:Tyrosine; D011388:Prolactin