MPL1, a novel phosphatase with leucine-rich repeats, is essential for proper ERK2 phosphorylation and cell motility

Eukaryot Cell. 2008 Jun;7(6):958-66. doi: 10.1128/EC.00442-07. Epub 2008 Apr 11.


The novel Dictyostelium phosphatase MPL1 contains six leucine-rich repeats at the amino-terminal end and a phosphatase domain at the carboxyl end. Similarly architectured phosphatases exist among other protozoa, such as Entamoeba histolytica, Leishmania major, and Trypanosoma cruzi. MPL1 was strongly induced after 5 h of development; ablation by homologous recombination led to defective streaming and aggregation during development. In addition, cyclic AMP (cAMP)-pulsed mpl1(-) cells showed reduced random and directional motility. At the molecular level, mpl1(-) cells displayed higher prestimulus and persistent poststimulus ERK2 phosphorylation in response to cAMP stimulation. Consistent with their phenotype of persistent ERK2 phosphorylation, mpl1(-) cells also displayed an aberrant pattern of cAMP production, resembling that of the regA(-) cells. Reintroduction of a full-length MPL1 into mpl1(-) cells restored aggregation, ERK2 regulation, random and directional motility, and cAMP production similar to wild-type cells. We propose that MPL1 is a novel phosphatase essential for proper regulation of ERK2 phosphorylation and optimal motility during development.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Dictyostelium / cytology
  • Dictyostelium / enzymology*
  • Dictyostelium / physiology
  • Eukaryota / enzymology
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Molecular Sequence Data
  • Movement
  • Phosphoric Monoester Hydrolases / chemistry*
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphorylation
  • Protein Structure, Tertiary
  • Protozoan Proteins / metabolism


  • Protozoan Proteins
  • Mitogen-Activated Protein Kinase 1
  • Phosphoric Monoester Hydrolases