| pubmed-article:16785309 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16785309 | lifeskim:mentions | umls-concept:C0021758 | lld:lifeskim |
| pubmed-article:16785309 | lifeskim:mentions | umls-concept:C0541150 | lld:lifeskim |
| pubmed-article:16785309 | lifeskim:mentions | umls-concept:C0010531 | lld:lifeskim |
| pubmed-article:16785309 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:16785309 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:16785309 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:16785309 | lifeskim:mentions | umls-concept:C1521840 | lld:lifeskim |
| pubmed-article:16785309 | pubmed:issue | 7 | lld:pubmed |
| pubmed-article:16785309 | pubmed:dateCreated | 2006-7-11 | lld:pubmed |
| pubmed-article:16785309 | 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. | lld:pubmed |
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| pubmed-article:16785309 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16785309 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16785309 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:16785309 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16785309 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:16785309 | pubmed:issn | 0022-1007 | lld:pubmed |
| pubmed-article:16785309 | pubmed:author | pubmed-author:WeissArthurA | lld:pubmed |
| pubmed-article:16785309 | pubmed:author | pubmed-author:PheeHyewonH | lld:pubmed |
| pubmed-article:16785309 | pubmed:author | pubmed-author:HoMaryM | lld:pubmed |
| pubmed-article:16785309 | pubmed:author | pubmed-author:NirulaAjayA | lld:pubmed |
| pubmed-article:16785309 | pubmed:author | pubmed-author:RooseJeroenJ | lld:pubmed |
| pubmed-article:16785309 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16785309 | pubmed:day | 10 | lld:pubmed |
| pubmed-article:16785309 | pubmed:volume | 203 | lld:pubmed |
| pubmed-article:16785309 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16785309 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16785309 | pubmed:pagination | 1733-44 | lld:pubmed |
| pubmed-article:16785309 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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