Linked Life Data

17126905

Source:http://linkedlifedata.com/resource/pubmed/id/17126905

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-1-22
pubmed:abstractText
P38 MAPK is a central mediator in cytokine signalling in human leukocytes. P38 MAPK is activated by phosphorylation of a conserved Thr180-X-Tyr182 motif by dual phosphorylation via the upstream kinases MKK3 and MKK6. Alternatively, P38 MAPK can be activated via autophosphorylation when associated with TAB1. In this study P38 MAPK phosphorylation and activation (measured via phosphorylation of P38 MAPK downstream target MK2) were investigated upon engagement of the GM-CSF- and TNFalpha-receptors expressed on both eosinophils and neutrophils. The MKK3/MKK6 pathway mediated neutrophil P38 MAPK activation after stimulation with TNFalpha (100U/ml) or GM-CSF (10(-10)M). Under these conditions the activation but not phosphorylation of P38 MAPK could be inhibited by SB203580 (10(-5)M or 10(-6)M). In eosinophils SB203580 (10(-6)M) inhibited both the phosphorylation and activation of P38 MAPK after stimulation with several doses of TNFalpha (10-10000 U/ml) or GM-CSF (10(-11) to 10(-9)M), indicating that P38 MAPK activation is mediated via autophosphorylation in eosinophils. This hypothesis was supported by the finding that in marked contrast to neutrophils, MKK3/MKK6 did not show enhanced phosphorylation in eosinophils after cytokine stimulation, but were constitutively phosphorylated. Therefore, the involvement of TAB1 was investigated with regard to this cytokine-induced autophosphorylation. Co-immunoprecipitation experiments showed that TAB1 was constitutively associated with P38 MAPK in eosinophils and neutrophils and that cytokine-induced autophosphorylated P38 MAPK was co-precipitated with TAB1. These findings are consistent with the hypothesis that cytokine-induced autophosphorylation of P38 MAPK in primary granulocytes depends on the interaction with TAB1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2492-6
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Differential regulation of TNFalpha and GM-CSF induced activation of P38 MAPK in neutrophils and eosinophils.
pubmed:affiliation
Department of Pulmonary Diseases, University Medical Center Utrecht (UMCU), Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
pubmed:publicationType
Journal Article