PMID- 22257123
OWN - NLM
STAT- MEDLINE
DCOM- 20120514
LR  - 20120328
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 443
IP  - 2
DP  - 2012 Apr 15
TI  - gamma-Enolase C-terminal peptide promotes cell survival and neurite outgrowth by 
      activation of the PI3K/Akt and MAPK/ERK signalling pathways.
PG  - 439-50
LID - 10.1042/BJ20111351 [doi]
AB  - gamma-Enolase, a glycolytic enzyme, is expressed specifically in neurons. It exerts 
      neurotrophic activity and has been suggested to regulate growth, differentiation, 
      survival and regeneration of neurons. In the present study, we investigated the 
      involvement of gamma-enolase in PI3K (phosphoinositide 3-kinase)/Akt and MAPK 
      (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) 
      signalling, the two pathways triggered predominantly by neurotrophic factors. 
      Whereas the PI3K/Akt pathway, rather than the MAPK/ERK pathway, is involved in 
      gamma-enolase-enhanced cell survival, gamma-enolase-stimulated neurite outgrowth requires 
      both pathways, i.e. the activation of both PI3K and ERK1/2, leading to subsequent 
      expression of the growth-cone-specific protein GAP-43 (growth-associated protein 
      of 43 kDa). MEK (MAPK/ERK kinase) and PI3K inhibition blocked or attenuated the 
      neurite outgrowth associated with dynamic remodelling of the actin-based 
      cytoskeleton. We show that gamma-enolase-mediated PI3K activation regulates RhoA 
      kinase, a key regulator of actin cytoskeleton organization. Moreover, the 
      inhibition of RhoA downstream effector ROCK (Rho-associated kinase) results in 
      enhanced gamma-enolase-induced neurite outgrowth, accompanied by actin polymerization 
      and its redistribution to growth cones. Our results show that gamma-enolase controls 
      neuronal survival, differentiation and neurite regeneration by activating the 
      PI3K/Akt and MAPK/ERK signalling pathways, resulting in downstream regulation of 
      the molecular and cellular processes of cytoskeleton reorganization and cell 
      remodelling, activation of transcriptional factors and regulation of the cell 
      cycle.
FAU - Hafner, Anja
AU  - Hafner A
AD  - Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
FAU - Obermajer, Natasa
AU  - Obermajer N
FAU - Kos, Janko
AU  - Kos J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Peptide Fragments)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
SB  - IM
MH  - Cell Differentiation
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Neurites/drug effects/*metabolism
MH  - Peptide Fragments/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphopyruvate Hydratase/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/*drug effects
EDAT- 2012/01/20 06:00
MHDA- 2012/05/15 06:00
CRDT- 2012/01/20 06:00
PHST- 2012/01/20 06:00 [entrez]
PHST- 2012/01/20 06:00 [pubmed]
PHST- 2012/05/15 06:00 [medline]
AID - BJ20111351 [pii]
AID - 10.1042/BJ20111351 [doi]
PST - ppublish
SO  - Biochem J. 2012 Apr 15;443(2):439-50. doi: 10.1042/BJ20111351.