Roles of the phosphatase POPX in the regulation of cell signalling and cell morphology.

Abstract

Rho GTPases and their downstream effectors regulate changes in the actin cytoskeleton that underlie cell motility and adhesion. They also participate in the regulation of gene transcription with RhoA activating serum response factor (SRF) mediated transcription from the serum response element (SRE). SRF-mediated transcription is also promoted by indentified a family of PP2C phosphatases, POPXs, which can dephosphorylate Cdc42/Rac-actived kinase PAK and down regulate its enzymatic and actin cytoskeletal activity. We now report that POPX interacts with the formin protein mDia. This interaction is enhanced when mDia is activated by RhoA. The binding of POPX to mDia-containing complex greatly decreases the ability of mDia to activate transcription from SRE. We propose that the interaction between mDia and POPX2 serves to regulate both the actin cytokeleton and SRF-mediated transcription, and to link Cdc42/Rac with RhoA pathways.