Mnk

Mitogen-activated protein kinase (MAPK) interacting protein kinases (Mnks) are a family of serine/threonine kinases. Mnks are downstream effectors of MAPK signaling, and have been implicated in oncogenic transformation and progression

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
4500 Cercosporamide
Potent Mnk2 inhibitor
2731 CGP 57380
Selective inhibitor of Mnk1
5183 ETP 45835 dihydrochloride
Mnk1 and Mnk2 inhibitor

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.

Literature for Mnk

Cancer

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Kinases

Kinases Product Listing

A collection of over 400 products for kinase research, the listing includes inhibitors of:

  • Receptor Tyrosine Kinases
  • Protein Kinases A, C, D and G
  • PI-3 Kinase, Akt and mTOR
  • MAPK Signaling
  • Receptor Serine/Threonine Kinases
MAPK Signaling

MAPK Signaling Scientific Review

MAP kinase signaling is integral to the regulation of numerous cellular processes such as proliferation and differentiation, and as a result is an important focus of cancer and immunology research. Updated for 2016, this review discusses the regulation of the MAPK pathway and properties of MAPK cascades. Compounds available from Tocris are listed.

Mnk Gene Data

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