IMR Press / FBL / Volume 13 / Issue 14 / DOI: 10.2741/3086

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases)
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1 Immunopathology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Doctor Aiguader 88, 08003 Barcelona, Spain
2 Medical Oncology Research Program, Vall d’Hebron University Hospital Research Institute, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
3 Department of Biochemistry and Molecular Biology, Life Sciences Centre, 2350 Health Sciences Mall, University of British Columbia, Vancouver, V6T 1Z3, BC, Canada

*Author to whom correspondence should be addressed.

Academic Editor: Matthias Gaestel

Front. Biosci. (Landmark Ed) 2008, 13(14), 5359–5373; https://doi.org/10.2741/3086
Published: 1 May 2008
(This article belongs to the Special Issue Protein kinase signaling downstream to MAPKs regulation)
Abstract

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. Mnk1a/b differ at their C-termini, as do Mnk2a/2b: in each case, the a-form possesses a longer C-terminal region than the b-form, which lacks the MAP kinase-binding region. The N-termini of all forms contain a polybasic region which binds importin α and the translation factor scaffold protein eukaryotic initiation factor (eIF) 4G. The catalytic domains of Mnk1a/b and Mnk2a/b share three unusual features: two short inserts and a DFD feature where other kinases have DFG. Mnk isoforms differ markedly in their activity and regulation, and in subcellular localization. The best-characterised Mnk substrate is eIF4E. The cellular role of eIF4E phosphorylation remains unclear: it may promote export of certain mRNAs from the nucleus. Other Mnk substrates bind to AU-rich elements that modulate the stability/translation of specific mRNAs. Mnks may also control production of inflammatory mediators and signaling from tyrosine kinase receptors, as well as cell proliferation or survival.

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