Gene interactions and pathways from curated databases and text-mining
Nature 1999, PMID: 10490027

Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP.

Yeung, K; Seitz, T; Li, S; Janosch, P; McFerran, B; Kaiser, C; Fee, F; Katsanakis, K D; Rose, D W; Mischak, H; Sedivy, J M; Kolch, W

Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK). This kinase cascade controls the proliferation and differentiation of different cell types. Here we describe a Raf-1-interacting protein, isolated using a yeast two-hybrid screen. This protein inhibits the phosphorylation and activation of MEK by Raf-1 and is designated RKIP (Raf kinase inhibitor protein). In vitro, RKIP binds to Raf-1, MEK and ERK, but not to Ras. RKIP co-immunoprecipitates with Raf-1 and MEK from cell lysates and colocalizes with Raf-1 when examined by confocal microscopy. RKIP is not a substrate for Raf-1 or MEK, but competitively disrupts the interaction between these kinases. RKIP overexpression interferes with the activation of MEK and ERK, induction of AP-1-dependent reporter genes and transformation elicited by an oncogenically activated Raf-1 kinase. Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK- and AP-1-dependent transcription. RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK module.

Diseases/Pathways annotated by Medline MESH: Cell Transformation, Neoplastic
Document information provided by NCBI PubMed

Text Mining Data

MEK-1 → Raf-1: " Raf-1 phosphorylates and activates MEK-1 , a kinase that activates the extracellular signal regulated kinases ( ERK ) "

ERK- ⊣ RKIP: " Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK- and AP-1 dependent transcription "

RKIP ⊣ AP-1: " Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK- and AP-1 dependent transcription "

Manually curated Databases

  • OpenBEL Selventa BEL large corpus: MAPK1 → MAP2K1 (directlyIncreases, MAP2K1 Activity, MAPK1 Activity)
    Evidence: Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK)
  • OpenBEL Selventa BEL large corpus: MAP2K1 → MAP2K1 (directlyIncreases, MAP2K1 Activity)
    Evidence: Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK)
  • OpenBEL Selventa BEL large corpus: MAP2K1 → RAF1 (directlyIncreases, RAF1 Activity, MAP2K1 Activity)
    Evidence: Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK)
  • OpenBEL Selventa BEL large corpus: MAP2K1 → RAF1 (directlyIncreases, MAP2K1 Activity)
    Evidence: Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK)
  • IRef Hprd Interaction: PEBP1 — MAPK1 (in vitro)
  • IRef Hprd Interaction: PEBP1 — MAPK1 (in vivo)
In total, 1 gene pairs are associated to this article in curated databases