RNA Recognition-like Motifs Activate a Mitogen-Activated Protein Kinase

Biochemistry. 2018 Dec 18;57(50):6878-6887. doi: 10.1021/acs.biochem.8b01032. Epub 2018 Dec 4.


Smk1 is a mitogen-activated protein kinase (MAPK) family member in the yeast Saccharomyces cerevisiae that controls the postmeiotic program of spore formation. Ssp2 is a meiosis-specific protein that activates Smk1 and triggers the autophosphorylation of its activation loop. A fragment of Ssp2 that is sufficient to activate Smk1 contains two segments that resemble RNA recognition motifs (RRMs). Mutations in either of these motifs eliminated Ssp2's ability to activate Smk1. In contrast, deletions and insertions within the segment linking the RRM-like motifs only partially reduced the activity of Ssp2. Moreover, when the two RRM-like motifs were expressed as separate proteins in bacteria, they activated Smk1. We also find that both motifs can be cross-linked to Smk1 and that at least one of the motifs binds near the ATP-binding pocket of the MAPK. These findings demonstrate that motifs related to RRMs can directly activate protein kinases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites / genetics
  • Enzyme Activation / genetics
  • Meiosis / genetics
  • Mitogen-Activated Protein Kinases / chemistry
  • Mitogen-Activated Protein Kinases / genetics*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Molecular
  • Mutation
  • Protein Conformation
  • RNA Recognition Motif / genetics*
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Spores, Fungal / genetics
  • Spores, Fungal / metabolism


  • RNA, Fungal
  • Recombinant Fusion Proteins
  • SSP2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Mitogen-Activated Protein Kinases
  • Smk1 protein, S cerevisiae