Dueling Kinases Regulate Cell Size at Division Through the SAD Kinase Cdr2

Curr Biol. 2014 Feb 17;24(4):428-33. doi: 10.1016/j.cub.2014.01.009. Epub 2014 Feb 6.

Abstract

Cell size control requires mechanisms that integrate cell growth and division. Key to this integration in fission yeast is the SAD family kinase Cdr2, which organizes a set of cortical nodes in the cell middle to promote mitotic entry through Wee1 and Cdk1. Cdr2 is inhibited by a spatial gradient of the DYRK kinase Pom1 emanating from cell tips in a cell-size-dependent manner, but how the Pom1 gradient inhibits Cdr2 activity during cell growth is unknown. Here, we show that Pom1 acts to prevent activation of Cdr2 kinase activity by the CaMKK Ssp1. We found that Ssp1 activates Cdr2 through phosphorylation of a conserved threonine residue (Thr166) in the activation loop of the Cdr2 N-terminal kinase domain both in vitro and in cells. The levels of this activating phosphorylation increased with cell-cycle progression, and genetic epistasis demonstrated that Ssp1 promotes mitotic entry through Cdr2. Intriguingly, Pom1 phosophorylated the C-terminal domain of Cdr2, and this modification reduced Cdr2-T166 phosphorylation by Ssp1. These findings show how activation of the conserved mitotic inducer Cdr2 is integrated with an inhibitory spatial gradient to ensure proper cell size control at mitosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Division
  • Cell Size
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • HSP70 Heat-Shock Proteins
  • PSS1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Protein Kinases
  • Pom1 protein, S pombe
  • Cdr2 protein, S pombe
  • Protein-Serine-Threonine Kinases