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.
Immunopathology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Doctor Aiguader 88, 08003 Barcelona, Spain.
Maria
M
Buxade
Josep L
JL
Parra-Palau
Christopher G
CG
Proud
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