PMID- 10490027
OWN - NLM
STAT- MEDLINE
DCOM- 19990927
LR  - 20111117
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 401
IP  - 6749
DP  - 1999 Sep 9
TI  - Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP.
PG  - 173-7
AB  - 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.
FAU - Yeung, K
AU  - Yeung K
AD  - Brown University, Department of Molecular Biology, Cell Biology and Biochemistry,
      Richmond 02912, USA.
FAU - Seitz, T
AU  - Seitz T
FAU - Li, S
AU  - Li S
FAU - Janosch, P
AU  - Janosch P
FAU - McFerran, B
AU  - McFerran B
FAU - Kaiser, C
AU  - Kaiser C
FAU - Fee, F
AU  - Fee F
FAU - Katsanakis, K D
AU  - Katsanakis KD
FAU - Rose, D W
AU  - Rose DW
FAU - Mischak, H
AU  - Mischak H
FAU - Sedivy, J M
AU  - Sedivy JM
FAU - Kolch, W
AU  - Kolch W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Androgen-Binding Protein)
RN  - 0 (Carrier Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Luminescent Proteins)
RN  - 0 (PEBP1 protein, human)
RN  - 0 (Phosphatidylethanolamine Binding Protein)
RN  - 0 (Phospholipid Transfer Proteins)
RN  - 0 (Prostatein)
RN  - 0 (Psbpc1 protein, rat)
RN  - 0 (Psbpc2 protein, rat)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Scgb2a2 protein, rat)
RN  - 0 (Secretoglobins)
RN  - 0 (Transcription Factor AP-1)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 9060-09-7 (Uteroglobin)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP3K1 protein, human)
RN  - EC 2.7.11.25 (Map3k1 protein, mouse)
SB  - IM
MH  - 3T3 Cells
MH  - *Androgen-Binding Protein
MH  - Animals
MH  - COS Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*antagonists & inhibitors/metabolism
MH  - Carrier Proteins/isolation & purification/*metabolism
MH  - Cell Transformation, Neoplastic
MH  - Cloning, Molecular
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/metabolism
MH  - Gene Expression Regulation
MH  - Green Fluorescent Proteins
MH  - Humans
MH  - Luminescent Proteins/genetics
MH  - *MAP Kinase Kinase Kinase 1
MH  - Mice
MH  - Phosphatidylethanolamine Binding Protein
MH  - Phospholipid Transfer Proteins
MH  - Prostatein
MH  - Protein-Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-raf/*antagonists & inhibitors/metabolism
MH  - Rats
MH  - Recombinant Proteins/genetics/metabolism
MH  - Secretoglobins
MH  - Signal Transduction/*drug effects
MH  - Transcription Factor AP-1/metabolism
MH  - Uteroglobin
EDAT- 1999/09/18 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/09/18 09:00
PHST- 1999/09/18 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/09/18 09:00 [entrez]
AID - 10.1038/43686 [doi]
PST - ppublish
SO  - Nature. 1999 Sep 9;401(6749):173-7. doi: 10.1038/43686.