Linked Life Data

20162623

Source:http://linkedlifedata.com/resource/pubmed/id/20162623

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-4-7
pubmed:abstractText
Activin A is a member of the transforming growth factor (TGF)-beta superfamily that regulates cell proliferation and differentiation. Using the p38 inhibitor SB203580, our previous studies demonstrated that p38 was involved in activin A-mediated hemoglobin (Hb) synthesis in K562 cells. SB203580 is an inhibitor of p38alpha and p38beta isoforms. In this study, we show that p38alpha and p38beta mRNA were expressed in K562 cells and that activin A activated the kinase activities of these isoforms. To investigate the roles of p38alpha and p38beta isoforms in activin A-mediated erythroid differentiation, we generated stable clones that over-expressed the dominant negative p38 isoforms p38alpha(AF) and p38beta(AF) in K562 cells. The expressions of either p38alpha(AF) or p38beta(AF) reduced activin A-induced p38 activation, Hb synthesis, and zeta-globin promoter activity. Similarly, down-regulation of either p38alpha or p38beta by isoform-specific siRNAs also reduced activin A-induced zeta-globin promoter activity. Co-expressions of p38alpha(AF) and p38beta(AF), together, greatly inhibited the transcription activity of the zeta-globin promoter. Conversely, expression of mitogen-activated protein kinase kinase (MKK) 6b(E), a constitutive activator of p38, significantly activated zeta-globin promoter. Co-expressions of either p38alpha or p38beta with MKK6b had a similar activation of zeta-globin promoter. Activin A induction of erythroid differentiation was inhibited by follistatin. Activin A-induced phosphorylation of MKK6 and p38 was also inhibited by follistatin. Moreover, over-expression of MKK6b(E) reverted follistatin inhibition of activin A-induced zeta-globin promoter activity. These results demonstrate that activin A induces erythroid differentiation of K562 cells through activation of MKK6-p38alpha/p38beta pathway and follistatin inhibits those effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1097-4652
pubmed:author
pubmed:copyrightInfo
(c) 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
223
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
687-94
pubmed:meshHeading
pubmed-meshheading:20162623-Activins, pubmed-meshheading:20162623-Cell Differentiation, pubmed-meshheading:20162623-Enzyme Activation, pubmed-meshheading:20162623-Erythroid Cells, pubmed-meshheading:20162623-Follistatin, pubmed-meshheading:20162623-Gene Expression Regulation, pubmed-meshheading:20162623-Gene Knockdown Techniques, pubmed-meshheading:20162623-Globins, pubmed-meshheading:20162623-Humans, pubmed-meshheading:20162623-Isoenzymes, pubmed-meshheading:20162623-K562 Cells, pubmed-meshheading:20162623-MAP Kinase Kinase 6, pubmed-meshheading:20162623-MAP Kinase Signaling System, pubmed-meshheading:20162623-Mitogen-Activated Protein Kinase 11, pubmed-meshheading:20162623-Mitogen-Activated Protein Kinase 14, pubmed-meshheading:20162623-Phosphorylation, pubmed-meshheading:20162623-Promoter Regions, Genetic
pubmed:year
2010
pubmed:articleTitle
Activin A induction of erythroid differentiation through MKK6-p38alpha/p38beta pathway is inhibited by follistatin.
pubmed:affiliation
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. cmbhhm@tmu.edu.tw
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't