PMID- 17003042
OWN - NLM
STAT- MEDLINE
DCOM- 20070109
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 47
DP  - 2006 Nov 24
TI  - Brain-derived neurotrophic factor activates ERK5 in cortical neurons via a 
      Rap1-MEKK2 signaling cascade.
PG  - 35965-74
AB  - The extracellular signal-regulated kinase 5 (ERK5) is activated in neurons of the 
      central nervous system by neurotrophins including brain-derived neurotrophic 
      factor (BDNF). Although MEK5 is known to mediate BDNF stimulation of ERK5 in 
      central nervous system neurons, other upstream signaling components have not been 
      identified. Here, we report that BDNF induces a sustained activation of ERK5 in 
      rat cortical neurons and activates Rap1, a small GTPase, as well as MEKK2, a MEK5 
      kinase. Our data indicate that activation of Rap1 or MEKK2 is sufficient to 
      stimulate ERK5, whereas inhibition of either Rap1 or MEKK2 attenuates BDNF 
      activation of ERK5. Furthermore, BDNF stimulation of MEKK2 is regulated by Rap1. 
      Our evidence also indicates that Ras and MEKK3, a MEK5 kinase in non-neuronal 
      cells, do not play a significant role in BDNF activation of ERK5. This study 
      identifies Rap1 and MEKK2 as critical upstream signaling molecules mediating BDNF 
      stimulation of ERK5 in central nervous system neurons.
FAU - Wang, Yupeng
AU  - Wang Y
AD  - Toxicology Program, Department of Environmental and Occupational Health Sciences, 
      University of Washington, Seattle, Washington 98195-7234, USA.
FAU - Su, Bing
AU  - Su B
FAU - Xia, Zhengui
AU  - Xia Z
LA  - eng
GR  - AG19193/AG/NIA NIH HHS/United States
GR  - P30 HD02274/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060926
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 7)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 2)
RN  - EC 2.7.11.25 (Map3k2 protein, mouse)
RN  - EC 3.6.5.2 (rap1 GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Brain/embryology
MH  - Brain-Derived Neurotrophic Factor/metabolism/*physiology
MH  - Central Nervous System/metabolism
MH  - Enzyme Activation
MH  - MAP Kinase Kinase Kinase 2/metabolism/*physiology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 7/*metabolism
MH  - Models, Biological
MH  - Neurons/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - rap1 GTP-Binding Proteins/metabolism/*physiology
EDAT- 2006/09/28 09:00
MHDA- 2007/01/11 09:00
CRDT- 2006/09/28 09:00
PHST- 2006/09/28 09:00 [pubmed]
PHST- 2007/01/11 09:00 [medline]
PHST- 2006/09/28 09:00 [entrez]
AID - S0021-9258(20)68146-7 [pii]
AID - 10.1074/jbc.M605503200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Nov 24;281(47):35965-74. doi: 10.1074/jbc.M605503200. Epub 2006 
      Sep 26.