MPL1, the novel phosphatase with Leucine-Rich-Repeats, is essential for proper ERK2 phosphorylation and cell motility

Dept of Biological Sciences, Florida International University, Miami, FL 33199

^* To whom correspondence should be addressed. Email: kiml{at}fiu.edu.

	Abstract

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 hours of development; ablation by homologous recombination led to defective streaming and aggregation during development. In addition, cAMP pulsed mpl1^- cells showed reduced random and directional motility. At the molecular level, mpl1^- cells displayed higher prestimulus and persistent post-stimulus 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.