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.View all products for Mnk »
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Literature for Mnk
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
- Invasion and Metastasis
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
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.Request copy | Download PDF | View all reviews
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