PMID- 22260667
OWN - NLM
STAT- MEDLINE
DCOM- 20120518
LR  - 20211021
IS  - 1470-8752 (Electronic)
IS  - 0300-5127 (Linking)
VI  - 40
IP  - 1
DP  - 2012 Feb
TI  - Regulation of MEK/ERK pathway output by subcellular localization of B-Raf.
PG  - 67-72
LID - 10.1042/BST20110621 [doi]
AB  - The strength and duration of intracellular signalling pathway activation is a key 
      determinant of the biological outcome of cells in response to extracellular cues. 
      This has been particularly elucidated for the Ras/Raf/MEK [mitogen-activated 
      growth factor/ERK (extracellular-signal-regulated kinase) kinase]/ERK signalling 
      pathway with a number of studies in fibroblasts showing that sustained ERK 
      signalling is a requirement for S-phase entry, whereas transient ERK signalling 
      does not have this capability. A major unanswered question, however, is how a 
      cell can sustain ERK activation, particularly when ERK-specific phosphatases are 
      transcriptionally up-regulated by the pathway itself. A major point of ERK 
      regulation is at the level of Raf, and, to sustain ERK activation in the presence 
      of ERK phosphatases, sustained Raf activation is a requirement. Three Raf 
      proteins exist in mammals, and the activity of all three is induced following 
      growth factor stimulation of cells, but only B-Raf activity is maintained at 
      later time points. This observation points to B-Raf as a regulator of sustained 
      ERK activation. In the present review, we consider evidence for a link between 
      B-Raf and sustained ERK activation, focusing on a potential role for the 
      subcellular localization of B-Raf in this key physiological event.
FAU - Andreadi, Catherine
AU  - Andreadi C
AD  - Department of Biochemistry, Henry Wellcome Building, University of Leicester, 
      Lancaster Road, Leicester LE1 9HN, UK.
FAU - Noble, Catherine
AU  - Noble C
FAU - Patel, Bipin
AU  - Patel B
FAU - Jin, Hong
AU  - Jin H
FAU - Aguilar Hernandez, Maria M
AU  - Aguilar Hernandez MM
FAU - Balmanno, Kathryn
AU  - Balmanno K
FAU - Cook, Simon J
AU  - Cook SJ
FAU - Pritchard, Catrin
AU  - Pritchard C
LA  - eng
GR  - BBS/E/B/0000C199/BB_/Biotechnology and Biological Sciences Research 
      Council/United Kingdom
GR  - C1362/A6969/CRUK_/Cancer Research UK/United Kingdom
GR  - 08-0412/AICR_/Worldwide Cancer Research/United Kingdom
GR  - 13083/CRUK_/Cancer Research UK/United Kingdom
GR  - BBS/E/B/000C0417/BB_/Biotechnology and Biological Sciences Research 
      Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Biochem Soc Trans
JT  - Biochemical Society transactions
JID - 7506897
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Nucleus/metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - *MAP Kinase Signaling System
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein Binding
MH  - *Protein Transport
MH  - Proto-Oncogene Proteins B-raf/chemistry/*metabolism
EDAT- 2012/01/21 06:00
MHDA- 2012/05/19 06:00
CRDT- 2012/01/21 06:00
PHST- 2012/01/21 06:00 [entrez]
PHST- 2012/01/21 06:00 [pubmed]
PHST- 2012/05/19 06:00 [medline]
AID - BST20110621 [pii]
AID - 10.1042/BST20110621 [doi]
PST - ppublish
SO  - Biochem Soc Trans. 2012 Feb;40(1):67-72. doi: 10.1042/BST20110621.