Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.3.23 (GAS)
 957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Site-directed mutagenesis of the three binding sites for the mammary factor MPBF in the beta-lactoglobulin (BLG) promoter demonstrates that MPBF is a transcriptional activator of the BLG gene in mammary cells. MPBF requires phosphorylation on tyrosine for maximum binding activity and binds to GAS (interferon gamma-activation site) elements which are similar to the MPBF binding sites. Prolactin induces MPBF binding activity in CHO cells and is not antigenically related to Stat1 (p91) and Stat2 (p113), suggesting that this transcription factor is likely to be another member of the STAT family of cytokine/growth factor-induced transcription factors.
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PMID:The mammary factor MPBF is a prolactin-induced transcriptional regulator which binds to STAT factor recognition sites. 752 Aug 71

Interferon (IFN)-alpha-activated Stat1 homodimers and Stat1-2 heterodimers bind to GAS elements, whereas the transcription factor ISGF3, which contains Stat1, Stat2 and p48, binds to ISREs. We now find that Stat1-2 dimers can form heterotetramers on tandem GAS sites and that the heterotetramers have a much higher binding affinity for a double GAS site than do heterodimers for a single site, suggesting cooperativity mediated through protein-protein interactions. Stat1-2 heterotetramers can also be detected with a single GAS site, again indicating cooperativity mediated through protein-protein interactions. Deleting 40 amino acid residues from the N-terminus of Stat1 abolished Stat1-Stat2 heterotetramer formation, but did not affect heterodimer formation and an N-terminal peptide containing the first 120 residues of Stat2 inhibited heterotetramer formation but did not affect heterodimer formation. Thus, the N-terminal regions of both Stat1 and Stat2 are important for cooperative DNA binding, and heterodimers probably interact with each other through these regions. Cooperative binding of ISGF3 was also observed using the tandem ISREs from the IFN-alpha responsive promoter of the 6-16 gene. A more abundant and larger complex was formed with a probe containing two ISREs than with a probe containing a single ISRE. The N-terminal regions of both Stat1 and Stat2 are important for the cooperative binding of ISGF3 to tandem ISREs but not to a single site. The cooperative DNA-binding activities of ISGF3 and Stat1-2 dimers are likely to contribute to the transcriptional activation of those IFN-alpha-responsive genes that have tandem DNA elements.
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PMID:Cooperative binding of Stat1-2 heterodimers and ISGF3 to tandem DNA elements. 986 92

Urokinase-type plasminogen activator (uPA) and its specific receptor (uPAR) act in concert to stimulate cytoplasmic signaling machinery and transcription factors responsible for cell migration and proliferation. Recently we demonstrated that uPA activates the Janus kinase/signal transducers and activators of transcription (Stat1) signaling in human vascular smooth muscle and endothelial cells. However, the important question whether other transcription factors of the Stat family, in addition to Stat1, are involved in the uPAR-related signaling has not been addressed. In this study, we demonstrate that Stat4 and Stat2, but not Stat3, Stat5, or Stat6, are rapidly activated in response to uPA. We demonstrate further that Stat4 and Stat2 rapidly and transiently translocate to the cell nucleus where they bind specifically to the regulatory DNA elements. Analysis of Stat complexes formed in response to uPA revealed a Stat2-Stat1 heterodimer, which lacks p48, a DNA-binding protein known to combine with Stat1-Stat2. This new uPA-induced Stat2-Stat1 heterodimer binds to GAS (the interferon-gamma activation site) distinct from the interferon-stimulated response element to which the p48 protein containing complexes generally bind. We conclude that uPA activates a specific and unusual subset of latent cytoplasmic transcription factors in human vascular smooth muscle cells that suggests a critical role of uPA in these cells.
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PMID:Urokinase induces activation and formation of Stat4 and Stat1-Stat2 complexes in human vascular smooth muscle cells. 1044 76

Type I interferons are pleiotropic cytokines that transduce signals via activation of multiple downstream signaling cascades, including the Jak-Stat pathway. Although the roles of Stat1 and Stat2 in Type I interferon signaling are well established, the roles that other Stat-family members play in the induction of IFN-responses remain to be defined. In previous studies, we have shown that Stat5 associates with the CrkL adapter and forms a signaling complex that binds DNA. In the present study, we provide evidence that Stat5 is phosphorylated on serines 725/730 in an IFNalpha- and IFNbeta-dependent manner, providing direct evidence that serine phosphorylation of the protein is a component of an interferon signaling cascade. Such serine phosphorylation of Stat5 is Map kinase- and PI 3(')-kinase independent, while the activation of the serine kinase that phosphorylates Stat5 is regulated by upstream tyrosine kinase activity. Using mouse embryonic fibroblasts with targeted disruption of the Stat5a and Stat5b genes, we demonstrate that full activation of Stat5 is required for Type I interferon-dependent gene transcription via GAS elements. Altogether, our data provide evidence that Stat5 plays an important role in IFN-signaling and participates in the induction of Type I IFN-dependent responses. Furthermore, our results strongly suggest that, in addition to phosphorylation on tyrosine residues, phosphorylation on serine residues exhibits regulatory effects on the transcriptional capacity of Stat5.
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PMID:Role of Stat5 in type I interferon-signaling and transcriptional regulation. 1290 72