Linked Life Data

10395662

Source:http://linkedlifedata.com/resource/pubmed/id/10395662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-7-29
pubmed:abstractText
We have investigated the role of the mitogen-activated protein kinase (MAPK) pathway in the differentiation of CD4+ and CD8+ T cells by looking specifically at the effects of inhibitors of MAPK-activating enzyme, MAPK/extracellular signal-related kinase (ERK) kinase (MEK), during the positive selection step from double-positive to single-positive (SP) thymocytes. Using a variety of transgenic/knockout mouse strain combinations that fail to differentiate individual lineages of SP thymocytes together with genetically engineered F(ab')2 reagents that induce maturation preferentially to either the CD4 or CD8 subpopulations, we show that induction of CD4 differentiation cells is highly sensitive to levels of MEK inhibition that have no effect on CD8 maturation. In addition, the presence of MEK inhibitor is able to modify signals that normally induce CD4 differentiation to instead promote CD8 differentiation. Finally, we show that continuous culture in the presence of inhibitor interferes with TCR up-regulation in SP thymocytes, suggesting that MAPK signaling may be involved in final maturation steps for both lineages. These data indicate that there is discrimination in the biochemical pathways that are necessary to specify CD4 and CD8 lineage commitment and can reconcile previously conflicting reports on the influence of MAPK activation in commitment and maturation of thymocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
715-22
pubmed:dateRevised
2010-8-25
pubmed:meshHeading
pubmed-meshheading:10395662-Animals, pubmed-meshheading:10395662-Antigens, CD3, pubmed-meshheading:10395662-Antigens, CD4, pubmed-meshheading:10395662-CD4-Positive T-Lymphocytes, pubmed-meshheading:10395662-CD8-Positive T-Lymphocytes, pubmed-meshheading:10395662-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:10395662-Cell Differentiation, pubmed-meshheading:10395662-Cell Lineage, pubmed-meshheading:10395662-Enzyme Activation, pubmed-meshheading:10395662-Enzyme Inhibitors, pubmed-meshheading:10395662-Female, pubmed-meshheading:10395662-Flavonoids, pubmed-meshheading:10395662-Immune Sera, pubmed-meshheading:10395662-Immunoglobulin Fragments, pubmed-meshheading:10395662-Lymphocyte Activation, pubmed-meshheading:10395662-Male, pubmed-meshheading:10395662-Mice, pubmed-meshheading:10395662-Mice, Knockout, pubmed-meshheading:10395662-Mice, Transgenic, pubmed-meshheading:10395662-Organ Culture Techniques, pubmed-meshheading:10395662-Signal Transduction, pubmed-meshheading:10395662-Thymus Gland
pubmed:year
1999
pubmed:articleTitle
Activation of the extracellular signal-related kinase/mitogen-activated protein kinase pathway discriminates CD4 versus CD8 lineage commitment in the thymus.
pubmed:affiliation
Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't