Drosophila Lk6 kinase controls phosphorylation of eukaryotic translation initiation factor 4E and promotes normal growth and development
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Drosophila Lk6 kinase controls phosphorylation of eukaryotic translation initiation factor 4E and promotes normal growth and development. / Arquier, Nathalie; Bourouis, Marc; Colombani, Julien; Léopold, Pierre.
In: Current biology : CB, Vol. 15, No. 1, 11.01.2005, p. 19-23.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Drosophila Lk6 kinase controls phosphorylation of eukaryotic translation initiation factor 4E and promotes normal growth and development
AU - Arquier, Nathalie
AU - Bourouis, Marc
AU - Colombani, Julien
AU - Léopold, Pierre
PY - 2005/1/11
Y1 - 2005/1/11
N2 - Eukaryotic initiation factor 4E (eIF4E) controls a crucial step of translation initiation and is critical for cell growth . Biochemical studies have shown that it undergoes a regulated phosphorylation by the MAP-kinase signal-integrating kinases Mnk1 and Mnk2 . Although the role of eIF4E phosphorylation in mammalian cells has remained elusive , recent work in Drosophila has established that it is required for growth and development . Here, we demonstrate that a previously identified Drosophila kinase called Lk6 is the functional homolog of mammalian Mnk kinases. We generated lk6 loss-of-function alleles and found that eIF4E phosphorylation is dramatically reduced in lk6 mutants. Importantly, lk6 mutants exhibit reduced viability, slower development, and reduced adult size, demonstrating that Lk6 function is required for organismal growth. Moreover, we show that uniform lk6 expression rescues the lethality of eIF4E hypomorphic mutants in an eIF4E phosphorylation site-dependent manner and that the two proteins participate in a common complex in Drosophila S2 cells, confirming the functional link between Lk6 and eIF4E. This work demonstrates that Lk6 exerts a tight control on eIF4E phosphorylation and is necessary for normal growth and development.
AB - Eukaryotic initiation factor 4E (eIF4E) controls a crucial step of translation initiation and is critical for cell growth . Biochemical studies have shown that it undergoes a regulated phosphorylation by the MAP-kinase signal-integrating kinases Mnk1 and Mnk2 . Although the role of eIF4E phosphorylation in mammalian cells has remained elusive , recent work in Drosophila has established that it is required for growth and development . Here, we demonstrate that a previously identified Drosophila kinase called Lk6 is the functional homolog of mammalian Mnk kinases. We generated lk6 loss-of-function alleles and found that eIF4E phosphorylation is dramatically reduced in lk6 mutants. Importantly, lk6 mutants exhibit reduced viability, slower development, and reduced adult size, demonstrating that Lk6 function is required for organismal growth. Moreover, we show that uniform lk6 expression rescues the lethality of eIF4E hypomorphic mutants in an eIF4E phosphorylation site-dependent manner and that the two proteins participate in a common complex in Drosophila S2 cells, confirming the functional link between Lk6 and eIF4E. This work demonstrates that Lk6 exerts a tight control on eIF4E phosphorylation and is necessary for normal growth and development.
KW - Amino Acid Sequence
KW - Animals
KW - Base Sequence
KW - Blotting, Western
KW - Body Weights and Measures
KW - Cells, Cultured
KW - Drosophila/genetics
KW - Drosophila Proteins
KW - Eukaryotic Initiation Factor-4E/metabolism
KW - Female
KW - Gene Expression
KW - Immunoprecipitation
KW - Larva/growth & development
KW - Mitogen-Activated Protein Kinase Kinases/genetics
KW - Molecular Sequence Data
KW - Mutagenesis
KW - Ovary/metabolism
KW - Phenotype
KW - Phosphorylation
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Sequence Alignment
KW - Sequence Analysis, DNA
KW - Transfection
U2 - 10.1016/j.cub.2004.12.037
DO - 10.1016/j.cub.2004.12.037
M3 - Journal article
C2 - 15649359
VL - 15
SP - 19
EP - 23
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 1
ER -
ID: 213552865