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MAP kinase interacting serine/threonine kinase 2

Mnk2, GPRK7, MKNK2
This gene encodes a member of the calcium/calmodulin-dependent protein kinases (CAMK) Ser/Thr protein kinase family, which belongs to the protein kinase superfamily. This protein contains conserved DLG (asp-leu-gly) and ENIL (glu-asn-ile-leu) motifs, and an N-terminal polybasic region which binds importin A and the translation factor scaffold protein eukaryotic initiation factor 4G (eIF4G). This protein is one of the downstream kinases activated by mitogen-activated protein (MAP) kinases. It phosphorylates the eukaryotic initiation factor 4E (eIF4E), thus playing important roles in the initiation of mRNA translation, oncogenic transformation and malignant cell proliferation. In addition to eIF4E, this protein also interacts with von Hippel-Lindau tumor suppressor (VHL), ring-box 1 (Rbx1) and Cullin2 (Cul2), which are all components of the CBC(VHL) ubiquitin ligase E3 complex. Multiple alternatively spliced transcript variants have been found, but the full-length nature and biological activity of only two variants are determined. These two variants encode distinct isoforms which differ in activity and regulation, and in subcellular localization. [provided by RefSeq, Aug 2011] (from NCBI)
Top mentioned proteins: Mnk1, ATP7B, eIF4E, p38, MAPK
Papers on Mnk2
Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood.
Kayser et al., Rotterdam, Netherlands. In J Biol Rhythms, Feb 2016
Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study.
Evaluation of mRNA markers for estimating blood deposition time: Towards alibi testing from human forensic stains with rhythmic biomarkers.
Kayser et al., Rotterdam, Netherlands. In Forensic Sci Int Genet, Jan 2016
We found that although in general mRNA-based estimation of time categories was less accurate than hormone-based estimation, the use of three mRNA markers HSPA1B, MKNK2 and PER3 together with melatonin and cortisol generally enhanced the time prediction accuracy relative to the use of the two hormones alone.
Inhibition of MAP Kinase-Interacting Kinase (MNK) Preferentially Affects Translation of mRNAs Containing both a 5'-Terminal Cap and Hairpin.
Rhoads et al., Shreveport, United States. In J Biol Chem, Jan 2016
UNASSIGNED: The mitogen-activated protein kinase-interacting kinases 1 and 2 (MNK1 and MNK2) are activated by extracellular-signal-regulated kinases 1 and 2 (ERK1/2) or p38 in response to cellular stress and extracellular stimuli that include growth factors, cytokines, and hormones.
Imbalanced splicing in MAPK signaling sustains Ras-induced transformation.
Pyronnet et al., Toulouse, France. In Clin Res Hepatol Gastroenterol, Apr 2015
The eIF4E factor is phosphorylated by MAPK-interacting protein kinases 1 and 2 (MNK1 and MNK2).
Identification and validation co-differentially expressed genes with NAFLD and insulin resistance.
Liu et al., Harbin, China. In Endocrine, Feb 2015
2. MAP kinase-interacting serine/threonine kinase 2 (Mknk2) was the unique gene to be identified that is involved in the insulin signaling pathway and Mitogen Activated Protein Kinase signaling pathway according to the Kyoto Encyclopedia of Genes and Genomes database.
Transcriptional analysis of left-sided colitis, pancolitis, and ulcerative colitis-associated dysplasia.
Olsen et al., Copenhagen, Denmark. In Inflamm Bowel Dis, 2014
Validation of selected transcripts hereof identified insulin receptor alpha (INSRA) and MAP kinase interacting serine/threonine kinase 2 (MKNK2) with an enhanced expression in dysplasia compared with left-sided UC and controls, whereas laminin γ2 (LAMC2) was found with a lower expression in dysplasia compared with the remaining 3 groups.
Identification of a gene expression driven progression pathway in myxoid liposarcoma.
Pilotti et al., Milano, Italy. In Oncotarget, 2014
In this model, a switch in the vascular landscape from a normal to a pro-angiogenic signature and the silencing of DLK1-DIO3 region mark the progression from ML to RC in concert with the acquisition by the latter of the over-expression of YYI/C-MYC/HDAC2, together with over-expression of genes involved in cell proliferation and stemness: MKNK2, MSX1 and TRIM71.
Mnk2 alternative splicing modulates the p38-MAPK pathway and impacts Ras-induced transformation.
Karni et al., Jerusalem, Israel. In Cell Rep, 2014
In humans, MKNK2, the gene encoding for Mnk2, is alternatively spliced yielding two splicing isoforms with differing last exons: Mnk2a, which contains a MAPK-binding domain, and Mnk2b, which lacks it.
MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven mRNA translation in DLBCL.
Gartenhaus et al., Baltimore, United States. In Nat Commun, 2013
The phosphorylation of eIF4E1 at serine 209 by MNK1 or MNK2 has been shown to initiate oncogenic mRNA translation, a process that favours cancer development and maintenance.
Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells.
Lin et al., Shenyang, China. In Mol Cancer, 2013
HE4 gene interference downregulated the expression of MAPK and the FOCAL adhesion signaling pathway-associated molecules MKNK2 and LAMB2, and HE4 protein supplementation reversed this effect.
Phosphorylation of serine 4,642 in the C-terminus of plectin by MNK2 and PKA modulates its interaction with intermediate filaments.
Borradori et al., Bern, Switzerland. In J Cell Sci, 2013
Using selective protein kinase inhibitors, we identified two different kinases that modulate the phosphorylation of plectin S4642 in HeLa cells: MNK2, which is downstream of the ERK1/2-dependent MAPK cascade, and PKA.
Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2/eIF4E pathway.
Sette et al., Roma, Italy. In Oncogene, 2013
RNA interference (RNAi) experiments indicated that MNK2 is mainly responsible for eIF4E phosphorylation and gemcitabine resistance in PDAC cells.
Oncogenic splicing factor SRSF1 is a critical transcriptional target of MYC.
Krainer et al., United States. In Cell Rep, 2012
In particular, MYC induction leads to SRSF1-mediated alternative splicing of the signaling kinase MKNK2 and the transcription factor TEAD1. SRSF1 knockdown reduces MYC's oncogenic activity, decreasing proliferation and anchorage-independent growth.
MNK2 inhibits eIF4G activation through a pathway involving serine-arginine-rich protein kinase in skeletal muscle.
Glass et al., Cambridge, United States. In Sci Signal, 2012
Data indicate that MNK2 plays a unique role, not shared by its closest paralog MNK1, in limiting protein translation through its negative effect on eIF4G Ser1108 phosphorylation and p70S6K activation.
Exploring aigialomycin d and its analogues as protein kinase inhibitors for cancer targets.
Chai et al., Singapore, Singapore. In Acs Med Chem Lett, 2011
Kinase profiling of aigialomycin D against a panel of kinases has led to the identification of MNK2 as a promising target (IC50 = 0.45 μM), and preliminary structure-activity relationship studies have been carried out to identify the essential functional groups for activity.
Essential role for Mnk kinases in type II interferon (IFNgamma) signaling and its suppressive effects on normal hematopoiesis.
Platanias et al., Chicago, United States. In J Biol Chem, 2011
siRNA-mediated Mnk1/2 knockdown results in partial reversal of the suppressive effects of IFNgamma on human CD34+-derived myeloid (CFU-GM) and erythroid (BFU-E) progenitors.
Differential contribution of the MTOR and MNK pathways to the regulation of mRNA translation in meiotic and postmeiotic mouse male germ cells.
Sette et al., Roma, Italy. In Biol Reprod, 2010
MAP kinase-interacting kinase 1 and 2 activity enhances formation of the EIF-4F complex in pachytene spermatocytes but not in round spermatids.
Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development.
Mak et al., Toronto, Canada. In Proc Natl Acad Sci U S A, 2010
oncogenic role for Mnk1/2 in tumor development
The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases).
Proud et al., Barcelona, Spain. In Front Biosci, 2007
The human MAP kinase-interacting kinases (or MAP kinase signal-integrating kinases), Mnks, comprise a group of four proteins derived from two genes (Gene symbols: MKNK1 and MKNK2) by alternative splicing.
Loss of MNK function sensitizes fibroblasts to serum-withdrawal induced apoptosis.
Sturgill et al., Charlottesville, United States. In Genes Cells, 2007
MNK1 and MNK2 are kinases involved in anti-apoptotic signaling in response to serum withdrawal
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