PMID- 10499589
OWN - NLM
STAT- MEDLINE
DCOM- 19991014
LR  - 20061120
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 401
IP  - 6750
DP  - 1999 Sep 16
TI  - EPS8 and E3B1 transduce signals from Ras to Rac.
PG  - 290-3
AB  - The small guanine nucleotide (GTP)-binding protein Rac regulates mitogen-induced 
      cytoskeletal changes and c-Jun amino-terminal kinase (JNK), and its activity is
      required for Ras-mediated cell transformation. Epistatic analysis placed Rac as a
      key downstream target in Ras signalling; however, the biochemical mechanism
      regulating the cross-talk among these small GTP-binding proteins remains to be
      elucidated. Eps8 (relative molecular mass 97,000) is a substrate of receptors
      with tyrosine kinase activity which binds, through its SH3 domain, to a protein
      designated E3b1/Abi-1. Here we show that Eps8 and E3b1/Abi-1 participate in the
      transduction of signals from Ras to Rac, by regulating Rac-specific guanine
      nucleotide exchange factor (GEF) activities. We also show that Eps8, E3b1 and
      Sos-1 form a tri-complex in vivo that exhibits Rac-specific GEF activity in
      vitro. We propose a model in which Eps8 mediates the transfer of signals between 
      Ras and Rac, by forming a complex with E3b1 and Sos-1.
FAU - Scita, G
AU  - Scita G
AD  - Department of Experimental Oncology, European Institute of Oncology, Milan,
      Italy.
FAU - Nordstrom, J
AU  - Nordstrom J
FAU - Carbone, R
AU  - Carbone R
FAU - Tenca, P
AU  - Tenca P
FAU - Giardina, G
AU  - Giardina G
FAU - Gutkind, S
AU  - Gutkind S
FAU - Bjarnegard, M
AU  - Bjarnegard M
FAU - Betsholtz, C
AU  - Betsholtz C
FAU - Di Fiore, P P
AU  - Di Fiore PP
LA  - eng
PT  - Journal Article
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (ABI1 protein, human)
RN  - 0 (Abi1 protein, mouse)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (EPS8 protein, human)
RN  - 0 (Eps8 protein, mouse)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Proteins)
RN  - 0 (ras Guanine Nucleotide Exchange Factors)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - 3T3 Cells
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - COS Cells
MH  - Carrier Proteins/*metabolism
MH  - Cloning, Molecular
MH  - Cytoskeletal Proteins
MH  - GTP Phosphohydrolases/metabolism
MH  - GTP-Binding Proteins/*metabolism
MH  - Genetic Vectors
MH  - Guanine Nucleotide Exchange Factors
MH  - Guanosine Triphosphate/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Protein Binding
MH  - Proteins/genetics/*metabolism
MH  - *Signal Transduction
MH  - rac GTP-Binding Proteins
MH  - ras Guanine Nucleotide Exchange Factors
MH  - ras Proteins/*metabolism
EDAT- 1999/09/28 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/09/28 09:00
PHST- 1999/09/28 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/09/28 09:00 [entrez]
AID - 10.1038/45822 [doi]
PST - ppublish
SO  - Nature. 1999 Sep 16;401(6750):290-3. doi: 10.1038/45822.