Nature 1999,
PMID: 10490027
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
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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
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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)
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IRef Hprd Interaction:
PEBP1
—
MAPK1
(in vivo)
In total, 1 gene pairs are associated to this article in curated databases