In the ciliate  Euplotes raikovi , a 631-amino acid  Er -MAPK1 protein kinase was found to localize in nucleoli of the transcriptionally active nucleus (macronucleus) and act as a key component of an autocrine, cell-growth promoting self-signaling mechanism. While its 283-amino acid N-terminal domain includes all the structural specificities of the mitogen-activated protein kinases required for a catalytic function, the 348-amino acid C-terminal domain is structurally unique with undetermined functions. By expressing the two  Er -MAPK1 domains tagged with the green fluorescent protein in mammalian fibroblasts, the yeast  Schizosaccharomyces pombe  and the ciliate  Tetrahymena thermophila , evidence was obtained that the C-terminal domain contains all the sequence information responsible for the  Er -MAPK1 subcellular localization. However, in fibroblasts and  S. pombe  this information determined a nucleolar localization of the GFP-tagged C-terminal domain, and a ciliary localization in  T. thermophila . In the light of these findings, the  Er -MAPK1 localization in  E. raikovi  was re-examined via immunoreactions and shown to be ciliary besides that nuclear, as is the case for the mammalian intestinal cell kinase with which the  Er -MAPK1 N-terminal domain shares a strong sequence identity and a catalytic function.