Gene interactions and pathways from curated databases and text-mining
Science 2005, PMID: 15802604

PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation.

Lee, Ki-Young; D'Acquisto, Fulvio; Hayden, Matthew S; Shim, Jae-Hyuck; Ghosh, Sankar

Activation of the transcription factor NF-kappaB after engagement of the T cell receptor (TCR) is important for T cell proliferation and activation during the adaptive immune response. Recent reports have elucidated a signaling pathway that involves the protein kinase C (PKC), the scaffold protein CARD11 (also called CARMA-1), the caspase recruitment domain (CARD)-containing protein Bcl10, and the paracaspase (protease related to caspases) MALT1 as critical intermediates linking the TCR to the IkappaB kinase (IKK) complex. However, the events proximal to the TCR that initiate the activation of this signaling pathway remain poorly defined. We demonstrate that 3-phosphoinositide-dependent kinase 1 (PDK1) has an essential role in this pathway by regulating the activation of PKC and through signal-dependent recruiting of both PKC and CARD11 to lipid rafts. PDK1-associated PKC recruits the IKK complex, whereas PDK1-associated CARD11 recruits the Bcl10-MALT1 complex, thereby allowing activation of the IKK complex through Bcl10-MALT1-dependent ubiquitination of the IKK complex subunit known as NEMO (NF-kappaB essential modifier). Hence, PDK1 plays a critical role by nucleating the TCR-induced NF-kappaB activation pathway in T cells.

Diseases/Pathways annotated by Medline MESH: Lymphoma, B-Cell, Marginal Zone
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Text Mining Data

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Manually curated Databases

  • IRef Bind Interaction: PDPK1 — PRKCQ
  • IRef Bind Interaction: IKBKG — IKBKB
  • IRef Bind Interaction: PDPK1 — CARD11
  • IRef Bind Interaction: IKBKG — PRKCQ
  • IRef Bind Interaction: PRKCQ — IKBKB
  • IRef Bind_translation Interaction: PDPK1 — PRKCQ (coimmunoprecipitation)
  • IRef Bind_translation Interaction: IKBKG — IKBKB (coimmunoprecipitation)
  • IRef Bind_translation Interaction: PDPK1 — CARD11 (coimmunoprecipitation)
  • IRef Bind_translation Interaction: CHUK — PRKCQ (coimmunoprecipitation)
  • IRef Bind_translation Interaction: IKBKG — PRKCQ (coimmunoprecipitation)
  • IRef Bind_translation Interaction: PRKCQ — IKBKB (coimmunoprecipitation)
  • IRef Biogrid Interaction: PRKCQ — PDPK1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: IKBKB — IKBKG (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CARD11 — PDPK1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CHUK — PRKCQ (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PRKCQ — IKBKG (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: IKBKB — PRKCQ (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: CARD11 — PDPK1 (in vivo)
  • IRef Hprd Interaction: CHUK — PRKCQ (in vivo)
  • IRef Hprd Interaction: PRKCQ — IKBKG (in vivo)
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PDK1/CARD11/BCL10/MALT1 complex (PDPK1-CARD11-BCL10-MALT1) → PDK1 (PDPK1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PDK1/CARD11/BCL10/MALT1 complex (PDPK1-CARD11-BCL10-MALT1) → MALT1 (MALT1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PDK1/CARD11/BCL10/MALT1 complex (PDPK1-CARD11-BCL10-MALT1) → BCL10 (BCL10) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PDK1/CARD11/BCL10/MALT1 complex (PDPK1-CARD11-BCL10-MALT1) → CARD11 (CARD11) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PDK1 (PDPK1) → MALT1 (MALT1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PDK1 (PDPK1) → BCL10 (BCL10) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PDK1 (PDPK1) → CARD11 (CARD11) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: MALT1 (MALT1) → BCL10 (BCL10) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: MALT1 (MALT1) → CARD11 (CARD11) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: BCL10 (BCL10) → CARD11 (CARD11) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PKC theta/FLNA complex (PRKCQ-FLNA) → PDK1/PKC theta complex (PDPK1-PRKCQ) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PKC theta/FLNA complex (PRKCQ-FLNA) → IKK complex complex (CHUK-IKBKB-IKBKG) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PDK1/PKC theta complex (PDPK1-PRKCQ) → IKK complex complex (CHUK-IKBKB-IKBKG) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PDK1 (PDPK1) → PKC theta (PRKCQ) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PDK1 (PDPK1) → PDK1/PKC theta complex (PDPK1-PRKCQ) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PKC theta (PRKCQ) → PDK1/PKC theta complex (PDPK1-PRKCQ) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PDK1 (PDPK1) → PKC theta (PRKCQ) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PDK1 (PDPK1) → PDK1/PKC theta complex (PDPK1-PRKCQ) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PKC theta (PRKCQ) → PDK1/PKC theta complex (PDPK1-PRKCQ) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database TCR signaling in naïve CD8+ T cells: PDK1/PKC theta complex (PDPK1-PRKCQ) → IKK complex complex (CHUK-IKBKB-IKBKG) (modification, activates)
    Evidence: mutant phenotype, other species
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PDK1/CARD11/BCL10/MALT1 complex (PDPK1-CARD11-BCL10-MALT1) → PDK1 (PDPK1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PDK1/CARD11/BCL10/MALT1 complex (PDPK1-CARD11-BCL10-MALT1) → CARD11 (CARD11) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PDK1/CARD11/BCL10/MALT1 complex (PDPK1-CARD11-BCL10-MALT1) → BCL10 (BCL10) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PDK1/CARD11/BCL10/MALT1 complex (PDPK1-CARD11-BCL10-MALT1) → MALT1 (MALT1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PDK1 (PDPK1) → CARD11 (CARD11) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PDK1 (PDPK1) → BCL10 (BCL10) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: PDK1 (PDPK1) → MALT1 (MALT1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: CARD11 (CARD11) → BCL10 (BCL10) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: CARD11 (CARD11) → MALT1 (MALT1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database TCR signaling in naïve CD4+ T cells: BCL10 (BCL10) → MALT1 (MALT1) (modification, collaborate)
    Evidence: physical interaction
In total, 26 gene pairs are associated to this article in curated databases