PMID- 10531364
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 44
DP  - 1999 Oct 29
TI  - Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control.
PG  - 31588-92
AB  - The activity of the catalytic domain of the orphan MAP kinase ERK5 is increased
      by Ras but not Raf-1 in cells, which suggests that ERK5 might mediate
      Raf-independent signaling by Ras. We found that Raf-1 does contribute to Ras
      activation of ERK5 but in a manner that does not correlate with Raf-1 catalytic
      activity. A clue to the mechanism of action of Raf-1 on ERK5 comes from the
      observation that endogenous Raf-1 binds to endogenous ERK5, suggesting the
      involvement of regulatory protein-protein interactions. This interaction is
      specific because Raf-1 binds only to ERK5 and not ERK2 or SAPK. Finally, we
      demonstrate the ERK5/MEK5 pathway is required for Raf-dependent cellular
      transformation and that a constitutively active form of MEK5, MEK5DD, synergizes 
      with Raf to transform NIH 3T3 cells. These observations suggest that ERK5 plays a
      large role in Raf-1-mediated signal transduction.
FAU - English, J M
AU  - English JM
AD  - Department of Pharmacology, The University of Texas Southwestern Medical Center, 
      Dallas, Texas 75235-9041, USA.
FAU - Pearson, G
AU  - Pearson G
FAU - Hockenberry, T
AU  - Hockenberry T
FAU - Shivakumar, L
AU  - Shivakumar L
FAU - White, M A
AU  - White MA
FAU - Cobb, M H
AU  - Cobb MH
LA  - eng
GR  - CA71443/CA/NCI NIH HHS/United States
GR  - DK34128/DK/NIDDK NIH HHS/United States
GR  - T32-CA66187/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 7)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 5)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - *Cell Transformation, Neoplastic
MH  - MAP Kinase Kinase 5
MH  - Mitogen-Activated Protein Kinase 7
MH  - Mitogen-Activated Protein Kinase Kinases/*metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-raf/*metabolism
MH  - Signal Transduction
MH  - ras Proteins/*metabolism
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1074/jbc.274.44.31588 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 29;274(44):31588-92. doi: 10.1074/jbc.274.44.31588.