| pubmed-article:16107690 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16107690 | lifeskim:mentions | umls-concept:C0014822 | lld:lifeskim |
| pubmed-article:16107690 | lifeskim:mentions | umls-concept:C1333663 | lld:lifeskim |
| pubmed-article:16107690 | lifeskim:mentions | umls-concept:C1530719 | lld:lifeskim |
| pubmed-article:16107690 | lifeskim:mentions | umls-concept:C0017337 | lld:lifeskim |
| pubmed-article:16107690 | lifeskim:mentions | umls-concept:C1334131 | lld:lifeskim |
| pubmed-article:16107690 | lifeskim:mentions | umls-concept:C0031621 | lld:lifeskim |
| pubmed-article:16107690 | lifeskim:mentions | umls-concept:C0145947 | lld:lifeskim |
| pubmed-article:16107690 | lifeskim:mentions | umls-concept:C0040624 | lld:lifeskim |
| pubmed-article:16107690 | lifeskim:mentions | umls-concept:C0100748 | lld:lifeskim |
| pubmed-article:16107690 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:16107690 | pubmed:issue | 17 | lld:pubmed |
| pubmed-article:16107690 | pubmed:dateCreated | 2005-8-18 | lld:pubmed |
| pubmed-article:16107690 | pubmed:abstractText | The contribution of erythropoietin to the differentiation of the red blood cell lineage remains elusive, and the demonstration of a molecular link between erythropoietin and the transcription of genes associated with erythroid differentiation is lacking. In erythroid cells, expression of the tissue inhibitor of matrix metalloproteinase (TIMP-1) is strictly dependent on erythropoietin. We report here that erythropoietin regulates the transcription of the TIMP-1 gene upon binding to its receptor in erythroid cells by triggering the activation of phosphatidylinositol 3-kinase (PI3K)/Akt. We found that Akt directly phosphorylates the transcription factor GATA-1 at serine 310 and that this site-specific phosphorylation is required for the transcriptional activation of the TIMP-1 promoter. This chain of events can be recapitulated in nonerythroid cells by transfection of the implicated molecular partners, resulting in the expression of the normally silent endogenous TIMP-1 gene. Conversely, TIMP-1 secretion is profoundly decreased in erythroid cells from fetal livers of transgenic knock-in mice homozygous for a GATA(S310A) gene, which encodes a GATA-1 mutant that cannot be phosphorylated at Ser(310). Furthermore, retrovirus-mediated expression of GATA(S310A) into GATA-1(null)-derived embryonic stem cells decreases the rate of hemoglobinization by more than 50% compared to expressed wild-type GATA-1. These findings provide the first example of a chain of coupling mechanisms between the binding of erythropoietin to its receptor and GATA-1-dependent gene expression. | lld:pubmed |
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| pubmed-article:16107690 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16107690 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16107690 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16107690 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16107690 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16107690 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:16107690 | pubmed:issn | 0270-7306 | lld:pubmed |
| pubmed-article:16107690 | pubmed:author | pubmed-author:LeboulchPhili... | lld:pubmed |
| pubmed-article:16107690 | pubmed:author | pubmed-author:OrkinStuart... | lld:pubmed |
| pubmed-article:16107690 | pubmed:author | pubmed-author:MayeuxPatrick... | lld:pubmed |
| pubmed-article:16107690 | pubmed:author | pubmed-author:RomeoPaul-Hen... | lld:pubmed |
| pubmed-article:16107690 | pubmed:author | pubmed-author:KadriZahraZ | lld:pubmed |
| pubmed-article:16107690 | pubmed:author | pubmed-author:RookeHeather... | lld:pubmed |
| pubmed-article:16107690 | pubmed:author | pubmed-author:ChretienStany... | lld:pubmed |
| pubmed-article:16107690 | pubmed:author | pubmed-author:Maouche-Chret... | lld:pubmed |
| pubmed-article:16107690 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16107690 | pubmed:volume | 25 | lld:pubmed |
| pubmed-article:16107690 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16107690 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16107690 | pubmed:pagination | 7412-22 | lld:pubmed |
| pubmed-article:16107690 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
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