PMID- 15487973
OWN - NLM
STAT- MEDLINE
DCOM- 20050729
LR  - 20181113
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 385
IP  - Pt 3
DP  - 2005 Feb 1
TI  - The Drosophila protein kinase LK6 is regulated by ERK and phosphorylates the 
      eukaryotic initiation factor eIF4E in vivo.
PG  - 695-702
AB  - In Drosophila cells, phosphorylation of eIF4E (eukaryotic initiation factor 4E) 
      is required for growth and development. In Drosophila melanogaster, LK6 is the 
      closest homologue of mammalian Mnk1 and Mnk2 [MAPK (mitogen-activated protein 
      kinase) signal-integrating kinases 1 and 2 respectively] that phosphorylate 
      mammalian eIF4E. Mnk1 is activated by both mitogen- and stress-activated 
      signalling pathways [ERK (extracellular-signal-regulated kinase) and p38 MAPK], 
      whereas Mnk2 contains a MAPK-binding motif that is selective for ERKs. LK6 
      possesses a binding motif similar to that in Mnk2. In the present study, we show 
      that LK6 can phosphorylate eIF4E at the physiological site. LK6 activity is 
      increased by the ERK signalling pathway and not by the stress-activated p38 MAPK 
      signalling pathway. Consistent with this, LK6 binds ERK in mammalian cells, and 
      this requires an intact binding motif. LK6 can bind to eIF4G in mammalian cells, 
      and expression of LK6 increases the phosphorylation of the endogenous eIF4E. In 
      Drosophila S2 Schneider cells, LK6 binds the ERK homologue Rolled, but not the 
      p38 MAPK homologue. LK6 phosphorylates Drosophila eIF4E in vitro. The 
      phosphorylation of endogenous eIF4E in Drosophila cells is increased by 
      activation of the ERK pathway but not by arsenite, an activator of p38 MAPK. RNA 
      interference directed against LK6 significantly decreases eIF4E phosphorylation 
      in Drosophila cells. These results show that LK6 binds to ERK and is activated by 
      ERK signalling and it is responsible for phosphorylating eIF4E in Drosophila.
FAU - Parra-Palau, Josep L
AU  - Parra-Palau JL
AD  - Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, 
      MSI/WTB Complex, Dow Street, Dundee DD1 5EH, UK.
FAU - Scheper, Gert C
AU  - Scheper GC
FAU - Harper, Daniel E
AU  - Harper DE
FAU - Proud, Christopher G
AU  - Proud CG
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 (Drosophila Proteins)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Eukaryotic Initiation Factor-4G)
RN  - 17885-08-4 (Phosphoserine)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.12.2 (Lk6 protein, Drosophila)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Cell Nucleus/enzymology
MH  - Cytoplasm/enzymology
MH  - Drosophila Proteins
MH  - Drosophila melanogaster/cytology/*enzymology/genetics/metabolism
MH  - Enzyme Activation/drug effects
MH  - Eukaryotic Initiation Factor-4E/genetics/*metabolism
MH  - Eukaryotic Initiation Factor-4G/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Humans
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/chemistry/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Phosphoserine/metabolism
MH  - Protein Binding
MH  - Tetradecanoylphorbol Acetate/pharmacology
PMC - PMC1134744
EDAT- 2004/10/19 09:00
MHDA- 2005/07/30 09:00
PMCR- 2005/08/01
CRDT- 2004/10/19 09:00
PHST- 2004/10/19 09:00 [pubmed]
PHST- 2005/07/30 09:00 [medline]
PHST- 2004/10/19 09:00 [entrez]
PHST- 2005/08/01 00:00 [pmc-release]
AID - BJ20040769 [pii]
AID - bj3850695 [pii]
AID - 10.1042/BJ20040769 [doi]
PST - ppublish
SO  - Biochem J. 2005 Feb 1;385(Pt 3):695-702. doi: 10.1042/BJ20040769.