Supporting information

Mitogen-activated protein kinase (MAPK) interacting protein kinases (Mnks) are a family of serine/threonine kinases of which there are four isoforms; Mnk1a, Mnk1b, Mnk2a and Mnk2b. Mnk1a/2a are downstream effectors of MAPK signaling, and have been implicated in oncogenic transformation and progression.

Structurally Mnk1a/2a consists of an N-terminal region that mediates protein localization, a catalytic domain and a C-terminus that contains a MAPK binding domain. The b isoforms differ slightly in that they lack the MAPK binding domain, and are therefore MAPK independent. Mnk1a/2a kinase activity is activated by the ERK and p38 MAPK signaling pathways, whilst PAK and PP2A have been shown to negatively regulate Mnk activity. Mnk effector proteins include the translation factor eukaryotic initiation factor 4E (eIF4E), hnRNPA1 which is involved in TNF-α translation, and cytosolic phospholipase A2 which catalyzes the release of the eicosanoid precursor arachidonic acid.

The most studied Mnk effector is eIF4E due its potential to preferentially enhance the translation of oncogenes including Mcl-1, c-Myc, cyclin D and VEGF. Activation of Mnk enhances its binding to the scaffolding protein eIF4G, where the kinase phosphorylates eIF4E, inducing eIF4E-mediated translation. Overexpression of eIF4E has been reported in many types of cancer, with Mnk-mediated phosphorylation of eIF4E being shown to be important for oncogenic transformation and the progression of tumorigenesis. Mnk has also been shown to mediate the production of proinflammatory cytokines such as TNF-α and IL-6, as well as mediating TGF-β-induced cell motility and cell cycle arrest.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Mnk1 Human MKNK1 NM_003684 Q9BUB5
Mouse Mknk1 NM_001285487 Q3V457
Rat Mknk1 NM_001044267 Q4G050
Mnk2 Human MKNK2 NM_199054 Q9HBH9
Mouse Mknk2 NM_021462 Q8CDB0
Rat Mknk2 NM_001011985 Q5U2N4

Literature for Mnk

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MAPK Signaling  Scientific Review

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Cancer Research Product Guide

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Our Cancer Research Guide highlights over 750 products for cancer research. Request copy or view PDF today.

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Kinase Inhibitor Toolbox

80 Kinase inhibitors
pre-dissolved in DMSO

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Kinases Product Listing

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Our Kinase listing highlights over 400 products for kinase research. Request copy or view PDF today.

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MAPK Signaling Review

Written by Aroon S. Karra and Melanie H. Cobb

MAPK Signaling  Scientific Review

Our MAPK signaling review gives an overview of the MAPK signaling cascade and summarizes small molecule inhibitors of the pathway. Request copy or view PDF today.

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26th ISN-ESN Biennal Meeting

26th ISN-ESN Biennial Meeting

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