ArticleThe Journal of experimental medicine2006
Phosphoinositide-dependent kinase 1 targets protein kinase A in a pathway that regulates interleukin 4.
Article in The Journal of experimental medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- The 3-phosphoinositide-dependent protein kinase 1 is an essential upstream activator of protein kinase A in malaria parasites.PLoS biology · 2021Article
- Protein kinases in Toxoplasma gondii.International journal for parasitology · 2021Review
- Glucocorticoids and myosin5b loss of function induce heightened PKA signaling in addition to membrane traffic defects.Molecular biology of the cell · 2019Article
- Phosphoinositide dependent protein kinase 1 is required for exercise-induced cardiac hypertrophy but not the associated mitochondrial adaptations.Journal of molecular and cellular cardiology · 2015Article
- Mechanisms of cyclic AMP/protein kinase A- and glucocorticoid-mediated apoptosis using S49 lymphoma cells as a model system.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- PI3K pathway inhibitors: potential prospects as adjuncts to vaccine immunotherapy for glioblastoma.Immunotherapy · 2014Review
- Functional mapping of protein kinase A reveals its importance in adult Schistosoma mansoni motor activity.PLoS neglected tropical diseases · 2013Article
- Cotranslational cis-phosphorylation of the COOH-terminal tail is a key priming step in the maturation of cAMP-dependent protein kinase.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Evolutionary Adaptations of Plant AGC Kinases: From Light Signaling to Cell Polarity Regulation.Frontiers in plant science · 2012Article
- Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278).Cellular and molecular life sciences : CMLS · 2011Article
- Yeast 3-phosphoinositide-dependent protein kinase-1 (PDK1) orthologs Pkh1-3 differentially regulate phosphorylation of protein kinase A (PKA) and the protein kinase B (PKB)/S6K ortholog Sch9.The Journal of biological chemistry · 2011Article
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- Development of QSAR model for immunomodulatory activity of natural coumarinolignoids.Drug design, development and therapy · 2010Article
- An enigmatic tail of CD28 signaling.Cold Spring Harbor perspectives in biology · 2010Review
- The nuts and bolts of AGC protein kinases.Nature reviews. Molecular cell biology · 2010Review
- Phosphoinositide (3,4,5)-triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates T-cell migration, not proliferation.Molecular and cellular biology · 2009Article
- A chimeric mechanism for polyvalent trans-phosphorylation of PKA by PDK1.Protein science : a publication of the Protein Society · 2009Article
- Targeted knock-in mice expressing mutations of CD28 reveal an essential pathway for costimulation.Molecular and cellular biology · 2009Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.