The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases).
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 a 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.
Buxade
Maria
M
Immunopathology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Doctor Aiguader 88, 08003 Barcelona, Spain.
Parra-Palau
Josep L
JL
Proud
Christopher G
CG
D017398:Alternative Splicing; D000818:Animals; D002470:Cell Survival; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D047908:Intracellular Signaling Peptides and Proteins; D011494:Protein Kinases; C491395:MKNK1 protein, human; C486342:MKNK2 protein, human; D017346:Protein Serine-Threonine Kinases