Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2
Andrew J. Waskiewicz,Andrea Flynn,Christopher G. Proud,Jonathan A. Cooper,Jonathan A. Cooper +4 more
TLDR
Mnk1 may define a convergence point between the growth factor‐activated and one of the stress‐activated protein kinase cascades and is a candidate to phosphorylate eIF‐4E in cells.Abstract:
Mitogen-activated protein (MAP) kinases bind tightly to many of their physiologically relevant substrates. We have identified a new subfamily of murine serine/threonine kinases, whose members, MAP kinase-interacting kinase 1 (Mnk1) and Mnk2, bind tightly to the growth factor-regulated MAP kinases, Erk1 and Erk2. MNK1, but not Mnk2, also binds strongly to the stress-activated kinase, p38. MNK1 complexes more strongly with inactive than active Erk, implying that Mnk and Erk may dissociate after mitogen stimulation. Erk and p38 phosphorylate MNK1 and Mnk2, which stimulates their in vitro kinase activity toward a substrate, eukaryotic initiation factor-4E (eIF-4E). Initiation factor eIF-4E is a regulatory phosphoprotein whose phosphorylation is increased by insulin in an Erk-dependent manner. In vitro, MNK1 rapidly phosphorylates eIF-4E at the physiologically relevant site, Ser209. In cells, Mnk1 is post-translationally modified and enzymatically activated in response to treatment with either peptide growth factors, phorbol esters, anisomycin or UV. Mitogen- and stress-mediated MNK1 activation is blocked by inhibitors of MAP kinase kinase 1 (Mkk1) and p38, demonstrating that Mnk1 is downstream of multiple MAP kinases. MNK1 may define a convergence point between the growth factor-activated and one of the stress-activated protein kinase cascades and is a candidate to phosphorylate eIF-4E in cells.read more
Citations
More filters
Journal ArticleDOI
Upstream and downstream of mTOR
Nissim Hay,Nahum Sonenberg +1 more
TL;DR: Both the upstream components of the signaling pathway(s) that activates mammalian TOR (mTOR) and the downstream targets that affect protein synthesis are described.
Journal ArticleDOI
Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions.
Gray W. Pearson,Fred L. Robinson,Tara Beers Gibson,Bing E. Xu,Mahesh Karandikar,Kevin S. Berman,Melanie H. Cobb +6 more
TL;DR: Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted and particular emphasis is on ERK1/2.
Journal ArticleDOI
Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation
John M. Kyriakis,Joseph Avruch +1 more
TL;DR: This review focuses on the biochemical components and regulation of mammalian stress-regulated mitogen-activated protein kinase (MAPK) pathways, and the nuclear factor-kappa B pathway, a second stress signaling paradigm.
Journal ArticleDOI
Mechanisms of type-I- and type-II-interferon-mediated signalling.
TL;DR: It is anticipated that an increased understanding of the contributions of these recently identified pathways will advance current thinking about how interferons work.
Journal ArticleDOI
Erk and p38 mapk-activated protein kinases: a family of protein kinases with diverse biological functions
Philippe P. Roux,John Blenis +1 more
TL;DR: The identities of the MK substrates indicate that they play important roles in diverse biological processes, including mRNA translation, cell proliferation and survival, and the nuclear genomic response to mitogens and cellular stresses.
References
More filters
Journal ArticleDOI
A novel genetic system to detect protein-protein interactions.
Stanley Fields,Ok-kyu Song +1 more
TL;DR: A novel genetic system to study protein-protein interactions between two proteins by taking advantage of the properties of the GAL4 protein of the yeast Saccharomyces cerevisiae, which may be applicable as a general method to identify proteins that interact with a known protein by the use of a simple galactose selection.
Journal ArticleDOI
The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.
TL;DR: Phylogenetic mapping of the conserved protein kinase catalytic domains can serve as a useful first step in the functional characterization of these newly identified family members.
Journal ArticleDOI
Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation
TL;DR: Experiments with PC12 cells suggest that the duration of ERK activation is critical for cell signaling decisions, and the extracellular signal-regulated kinase (ERK-regulated) MAPK pathway may be sufficient for these cellular responses.
Journal ArticleDOI
A protein kinase involved in the regulation of inflammatory cytokine biosynthesis.
Joseph C. Lee,Jeffrey T. Laydon,Peter C. McDonnell,Timothy Gallagher,Sanjay Kumar,David W. Green,Dean E. McNulty,M. J. Blumenthal,J. R. Heys,S. W. Landvatter,James E. Strickler,Megan M. McLaughlin,I. R. Siemens,Seth M. Fisher,George P. Livi,John R. White,Jerry L. Adams,Peter Young +17 more
TL;DR: Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds, suggesting that the CSBPs are critical for cytokine production.
Journal ArticleDOI
JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain
Benoit Dérijard,Benoit Dérijard,Masahiko Hibi,I-Huan Wu,I-Huan Wu,Tamera Barrett,Bing Su,Tiliang Deng,Michael Karin,Roger J. Davis,Roger J. Davis +10 more
TL;DR: JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation and its properties indicate that JNK1 activation may play an important role in tumor promotion.
Related Papers (5)
MNK1, a new MAP kinase‐activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates
Rikiro Fukunaga,Tony Hunter +1 more