Identification of the human Mnk2 gene (MKNK2) through protein interaction with estrogen receptor beta

We have identified and characterized the human Mnk2 gene (HGMW-approved gen e symbol MKNK2) through a yeast two-hybrid screen in which the Mnk2 protein interacted with the ligand-binding domain of estrogen receptor beta (ER be ta), Human Mnk2 is homologous to murine Mnk2 (similar to 94% identical) and human Mnk1 (71% identical), both of which encode MAP kinase interacting ki nases that are phosphorylated and activated by ERK1 and 2. This report pres ents a thorough genomic sequence analysis revealing that the human Mnk2 gen e has two C-terminal splice variants, designated here as Mnk2a and Mnk2b. T hese two isoforms are identical over the first 385 amino acids of the codin g sequence and differ only in the final exon which encodes an additional 80 residues for Mnk2a and 29 residues for Mnk2b. A more detailed biological a nalysis in yeast showed that the Mnk2 interaction was selective for ER beta as opposed to ER alpha and that the interaction was specific to Mnk2b as o pposed to Mnk2a or Mnk1. This pattern was reproduced in a mammalian two-hyb rid system using a completely different set of fusion partners; and in both yeast and mammalian systems, the addition of estradiol decreased the inter action. While it remains unknown whether ER beta is a substrate of Mnk2, th e interaction of these two proteins is reminiscent of ER alpha and ribosoma l S6 kinase (p90RSK), another MAP kinase-regulated kinase homologous to Mnk 2 that is known to phosphorylate ER alpha. (C) 2000 Academic Press.