← Back to Search
The MTOR/PI3K And MAPK Pathways Converge On EIF4B To Control Its Phosphorylation And Activity
D. Shahbazian, Philippe P Roux, V. Mieulet, M. Cohen, B. Raught, J. Taunton, J. B. Hershey, J. Blenis, M. Pende, N. Sonenberg
Published 2006 · Biology, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
The eukaryotic translation initiation factor 4B (eIF4B) plays a critical role in recruiting the 40S ribosomal subunit to the mRNA. In response to insulin, eIF4B is phosphorylated on Ser422 by S6K in a rapamycin‐sensitive manner. Here we demonstrate that the p90 ribosomal protein S6 kinase (RSK) phosphorylates eIF4B on the same residue. The relative contribution of the RSK and S6K modules to the phosphorylation of eIF4B is growth factor‐dependent, and the two phosphorylation events exhibit very different kinetics. The S6K and RSK proteins are members of the AGC protein kinase family, and require PDK1 phosphorylation for activation. Consistent with this requirement, phosphorylation of eIF4B Ser422 is abrogated in PDK1 null embryonic stem cells. Phosphorylation of eIF4B on Ser422 by RSK and S6K is physiologically significant, as it increases the interaction of eIF4B with the eukaryotic translation initiation factor 3.
This paper references
Cooperative Regulation of the Cell Division Cycle by the Protein Kinases RAF and AKT
A. Mirza (2004)
Signal transduction via the MAP kinases: proceed at your own RSK.
J. Blenis (1993)
Peptide and Protein Library Screening Defines Optimal Substrate Motifs for AKT/PKB*
T. Obata (2000)
Role of S6 phosphorylation and S6 kinase in cell growth.
S. Volarević (2001)
eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation.
A. Gingras (1999)
ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions
Philippe P Roux (2004)
The role of 3-phosphoinositide-dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells
Michayla R. Williams (2000)
A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay
M. Ferraiuolo (2005)
R. Walgate (1985)
A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3.
N. Méthot (1996)
PDK1, the master regulator of AGC kinase signal transduction.
A. Mora (2004)
RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1.
P. E. Burnett (1998)
Involvement of proteasome alpha-subunit PSMA7 in hepatitis C virus internal ribosome entry site-mediated translation.
M. Krueger (2001)
3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro
D. Alessi (1998)
Phosphorylation and Functional Inactivation of TSC2 by Erk Implications for Tuberous Sclerosisand Cancer Pathogenesis
L. Ma (2005)
2 The Pathway and Mechanism of Initiation of Protein Synthesis
J. Hershey (2000)
A phosphoserine‐regulated docking site in the protein kinase RSK2 that recruits and activates PDK1
M. Frödin (2000)
Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer
L Ma (2005)
Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with the proteolysis of a 220,000-dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex.
D. Etchison (1982)
Two structural domains of initiation factor eIF-4B are involved in binding to RNA.
T. Naranda (1994)
Signaling control of mRNA translation in cancer pathogenesis
E. Holland (2004)
6 Regulation of Ribosomal Recruitment in Eukaryotes
B. Raught (2000)
Disruption of the p70s6k/p85s6k gene reveals a small mouse phenotype and a new functional S6 kinase
H. Shima (1998)
Molecular Cross-talk between MEK1/2 and mTOR Signaling during Recovery of 293 Cells from Hypertonic Stress*
S. Naegele (2004)
90-kDa Ribosomal S6 Kinase Is Phosphorylated and Activated by 3-Phosphoinositide-dependent Protein Kinase-1*
C. J. Jensen (1999)
Dissociation of double-stranded polynucleotide helical structures by eukaryotic initiation factors, as revealed by a novel assay.
T. G. Lawson (1989)
Assembly of 48S Translation Initiation Complexesfrom Purified Components with mRNAs That Have Some Base Pairingwithin Their 5′ UntranslatedRegions
Sergei E Dmitriev (2003)
Structural Bioinformatics-Based Design of Selective, Irreversible Kinase Inhibitors
M. Cohen (2005)
Metabotropic glutamate receptor-initiated translocation of protein kinase p90rsk to polyribosomes: a possible factor regulating synaptic protein synthesis.
F. Angenstein (1998)
Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase.
Philippe P Roux (2004)
Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases
B. Raught (2004)
Structural Bioinformatics-Based Design of Selective , Irreversible Kinase Inhibitors
D. Daley (2005)
Regulation of elongation factor 2 kinase by p90RSK1 and p70 S6 kinase
X. Wang (2001)
Evidence That 3-Phosphoinositide-dependent Protein Kinase-1 Mediates Phosphorylation of p70 S6 Kinase in Vivoat Thr-412 as well as Thr-252*
A. Balendran (1999)
Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation
T. Miyazaki (1995)
In vivo role of the PIF‐binding docking site of PDK1 defined by knock‐in mutation
Barry J. Collins (2003)
Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction
M. Frödin (1999)
Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors.
B. Dasgupta (2005)
Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F.
F. Rozen (1990)
Eukaryotic protein synthesis initiation factor eIF-3: determination of concentration and association with ribosomes in rabbit reticulocyte and HeLa cell lysates.
G. Mengod (1985)
Inactivation of Glycogen Synthase Kinase-3 by Epidermal Growth Factor Is Mediated by Mitogen-activated Protein Kinase/p90 Ribosomal Protein S6 Kinase Signaling Pathway in NIH/3T3 Cells (*)
H. Eldar-Finkelman (1995)
Recent advances in the regulation of the TOR pathway by insulin and nutrients
J. Avruch (2005)
mTOR and S6K1 Mediate Assembly of the Translation Preinitiation Complex through Dynamic Protein Interchange and Ordered Phosphorylation Events
M. Holz (2005)
Regulation of Ribosomal S6 Kinase 2 by Mammalian Target of Rapamycin*
In-Hyun Park (2002)
Regulation of Ribosomal S6 Protein Kinase-p90rsk, Glycogen Synthase Kinase 3, and β-Catenin in Early Xenopus Development
M. Torres (1999)
Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to polysomes.
V. Rajasekhar (2003)
MS Cohen (2005)
Growth-factor-dependent mitogenesis requires two distinct phases of signalling
S. Jones (2001)
S6K1−/−/S6K2−/− Mice Exhibit Perinatal Lethality and Rapamycin-Sensitive 5′-Terminal Oligopyrimidine mRNA Translation and Reveal a Mitogen-Activated Protein Kinase-Dependent S6 Kinase Pathway
M. Pende (2004)
The PIF‐binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB
R. Biondi (2001)
Protein synthesis initiation factors from human HeLa cells and rabbit reticulocytes are similar: comparison of protein structure, activities, and immunochemical properties.
M. L. Brown-Luedi (1982)
Mechanism of activation of protein kinase B by insulin and IGF‐1.
D. Alessi (1996)
MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products.
J. Duncia (1998)
Mutational analysis of a DEAD box RNA helicase: the mammalian translation initiation factor eIF‐4A.
A. Pause (1992)
A 110-Kilodalton Subunit of Translation Initiation Factor eIF3 and an Associated 135-kilodalton Protein Are Encoded by theSaccharomyces cerevisiae TIF32 and TIF31Genes*
H. Vornlocher (1999)
Comparison of the specificities of p70 S6 kinase and MAPKAP kinase‐1 identifies a relatively specific substrate for p70 S6 kinase: the N‐terminal kinase domain of MAPKAP kinase‐1 is essential for peptide phosphorylation
Ian A. Leighton (1995)
This paper is referenced by
Interferon-Dependent Engagement of Eukaryotic Initiation Factor 4B via S6 Kinase (S6K)- and Ribosomal Protein S6K-Mediated Signals
B. Kroczynska (2009)
The effect of nighttime macronutrient choice and exercise training on body composition, strength, cardiovascular health, resting metabolism, and appetite in overweight and obese adults
Wyatt R Eddy (2012)
The p 90 RSK Family Members : Common Functions and Isoform Speci fi city
R. Lara (2013)
Mutant p53 proteins alter signaling pathways involved in autophagy and redox regulation in cancer cells
M. Cordani (2017)
Human Cytomegalovirus Strategies to Maintain and Promote mRNA Translation
Heather A. Vincent (2016)
TNFα affects CREB-mediated neuroprotective signaling pathways of synaptic plasticity in neurons as revealed by proteomics and phospho-proteomics.
P. Jensen (2017)
Light stimuli and circadian clock affect neural development in Drosophila melanogaster
Eleni Dapergola (2020)
Mammalian target of rapamycin complex 1: signalling inputs, substrates and feedback mechanisms.
E. Dunlop (2009)
The metabolic and functional consequences of hyperammonaemia
D. Wilkinson (2012)
Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB
Giuseppe Fiume (2013)
Muscarinic acetylcholine receptors mediate eIF4B phosphorylation in SNU-407 colon cancer cells.
Z. Liu (2016)
Distinct signalling properties of insulin receptor substrate (IRS)-1 and IRS-2 in mediating insulin/IGF-1 action.
Atefeh Rabiee (2018)
A Gene Expression Signature of Acquired Chemoresistance to Cisplatin and Fluorouracil Combination Chemotherapy in Gastric Cancer Patients
H. Kim (2011)
Rheb Inhibits Protein Synt hesis by Activating the PERK-eIF 2 a Signaling Cascade Graphical
R. Tyagi ()
Dengue virus-induced regulation of the host cell translational machinery.
C. S. Villas-Bôas (2009)
Convergence of synaptic pathophysiology in the hippocampus of Fmr1-/y and Syngap1+/- mice
S. Barnes (2015)
Mutations in CHMP2B in Lower Motor Neuron Predominant Amyotrophic Lateral Sclerosis (ALS)
L. Cox (2010)
Investigating the cellular mechanisms that determine RNMT dependency in breast cancer cells
Shanade Dunn (2014)
Regulatory Effects of Ribosomal S6 Kinase 1 (RSK1) in IFNλ Signaling*
B. Kroczynska (2010)
Signaling Pathways in Cancer
D. Kalderon (2008)
Dependent Translation Initiation in Breast Cancer Cells − Metformin Inhibits Mammalian Target of Rapamycin
R. Dowling (2007)
Gastrodin protects against cardiac hypertrophy and fibrosis
Chunming ShuChanggui (2012)
Many roads from mTOR to eIF 4 F
C. Thoreen (2013)
Ribosomal Protein Mutations Induce Autophagy through S6 Kinase Inhibition of the Insulin Pathway
H. Heijnen (2014)
USP 9 X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4 A 1
Zeng-xia Li (2018)
Targeting the receptor tyrosine kinase RET sensitizes breast cancer cells to tamoxifen treatment and reveals a role for RET in endocrine resistance
I. Plaza-Menacho (2010)
Dynamic Regulation of the Translation Initiation Helicase Complex by Mitogenic Signal Transduction to Eukaryotic Translation Initiation Factor 4G
M. Dobrikov (2012)
Insect cold hardiness: the role of mitogen‐activated protein kinase and Akt signalling in freeze avoiding larvae of the goldenrod gall moth, Epiblema scudderiana
J. Zhang (2017)
Cellular Differences in Protein Synthesis Regulate Tissue Homeostasis
M. Buszczak (2014)
Metastasis-associated gene, mag-1 improves tumour microenvironmental adaptation and potentiates tumour metastasis
Yan Wang (2012)
The molecular basis of translational control.
C. Fraser (2009)
Ecdysone control of developmental transitions: lessons from Drosophila research.
N. Yamanaka (2013)See more