Linked Life Data

10194762

Source:http://linkedlifedata.com/resource/pubmed/id/10194762

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-5-27
pubmed:abstractText
Serine phosphorylation of signal transducers and activators of transcription (STAT) 1 and 3 modulates their DNA-binding capacity and/or transcriptional activity. Earlier we suggested that STAT5a functional capacity could be influenced by the mitogen-activated protein kinase (MAPK) pathway. In the present study, we have analyzed the interactions between STAT5a and the MAPKs, extracellular signal-regulated kinases ERK1 and ERK2. GH treatment of Chinese hamster ovary cells stably transfected with the GH receptor (CHOA cells) led to rapid and transient activation of both STAT5a and ERK1 and ERK2. Pretreatment of cells with colchicine, which inhibits tubulin polymerization, did not inhibit STAT5a translocation to the nucleus and ERK1/2 activation. In vitro precipitation with a glutathione-S-transferase-fusion protein containing the C-terminal transactivation domain of STAT5a showed GH-regulated association of ERK1/2 with the fusion protein, while this was not seen when serine 780 in STAT5a was changed to alanine. In vitro phosphorylation of the glutathione-S-transferase-fusion proteins using active ERK only worked when the fusion protein contained wild-type STAT5a sequence. The same experiment, performed with full-length wild-type STAT5a and the corresponding S780A mutant, showed that serine 780 is the only substrate in full-length STAT5a for active ERK. In coimmunoprecipitation experiments, larger amounts of STAT5a-ERK1/2 complexes were detected in cytosol from untreated CHOA cells than in cytosol from GH-treated cells, suggesting the presence of preformed STAT5a-ERK1/2 complexes in unstimulated cells. Transfection experiments with COS cells showed that kinase-inactive ERK1 decreased GH stimulation of STAT5-regulated reporter gene expression. These observations show, for the first time, direct physical interaction between ERK and STAT5a and also clearly identify serine 780 as a target for ERK. Furthermore, it is also established that serine phosphorylation of STAT5a transactivation domain, via the MAPK pathway, is a means of modifying GH-induced transcriptional activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
555-65
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10194762-Animals, pubmed-meshheading:10194762-Biological Transport, pubmed-meshheading:10194762-CHO Cells, pubmed-meshheading:10194762-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:10194762-Cell Nucleus, pubmed-meshheading:10194762-Chemical Precipitation, pubmed-meshheading:10194762-Cricetinae, pubmed-meshheading:10194762-DNA-Binding Proteins, pubmed-meshheading:10194762-Enzyme Activation, pubmed-meshheading:10194762-Human Growth Hormone, pubmed-meshheading:10194762-Microtubules, pubmed-meshheading:10194762-Milk Proteins, pubmed-meshheading:10194762-Peptide Fragments, pubmed-meshheading:10194762-Phosphorylation, pubmed-meshheading:10194762-Recombinant Proteins, pubmed-meshheading:10194762-STAT5 Transcription Factor, pubmed-meshheading:10194762-Serine, pubmed-meshheading:10194762-Trans-Activators
pubmed:year
1999
pubmed:articleTitle
Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a.
pubmed:affiliation
Department of Medical Nutrition, Karolinska Institute, Novum, Huddinge, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't