Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-7-11
pubmed:abstractText
CD28 plays a critical role in T cell immune responses. Although the kinase Akt has been shown to act downstream of CD28 in T helper (Th)1 cytokine induction, it does not induce Th2 cytokines such as interleukin 4 (IL-4). We recently reported that phosphoinositide-dependent kinase 1 (PDK1) partially corrects the defect in IL-4 production present in CD28-deficient T cells, suggesting that PDK1 regulates IL-4 independently of Akt. We now describe a signaling pathway in which PDK1 targets IL-4 in the murine Th2 cell line D10. PDK1-mediated activation of this pathway is dependent on protein kinase A (PKA) and the nuclear factor of activated T cells (NFAT) P1 transcriptional element in the IL-4 promoter. PDK1 localizes to the immune synapse in a phosphatidylinositol 3-kinase-dependent manner, partially colocalizes with PKA at the synapse, and physically interacts with PKA. In RNA interference knockdown experiments, PDK1 is necessary for phosphorylation of PKA in T cells, as well as for activation of the IL-4 NFAT P1 element by the T cell receptor (TCR) and CD28. Phosphorylation of the critical PKA threonine residue is stimulated by engagement of TCR/CD28 via a PDK1-dependent mechanism. These findings together define a pathway linking the kinases PDK1 and PKA in the induction of the Th2 cytokine IL-4.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-10364160, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-10430626, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-10455013, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-10611249, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-10698939, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-10725744, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-10801415, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-11057891, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-11121747, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-11135576, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-11244036, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-11282019, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-11500365, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-11589697, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-11740499, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-11937535, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-12110585, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-12122038, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-12169624, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-12172960, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-12372837, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-12534554, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-12912918, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-15004555, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-15077109, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-15096485, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-15100285, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-15116068, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-15457207, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-15470025, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-15611161, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-15802604, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-1846244, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-2174560, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-7509360, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-7584133, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-7688139, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-8164687, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-8245456, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-8336717, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-8396727, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-8397339, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-8415766, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-8496684, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-8557518, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-8674125, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-8992981, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-9150141, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-9160750, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-9228007, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-9462518, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-9488457, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-9637919, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-9686601, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-9707564, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-9748166, http://linkedlifedata.com/resource/pubmed/commentcorrection/16785309-9829977
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1007
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
203
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1733-44
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
More...