Protein phosphatase 6 promotes transforming growth factor-β signaling in mouse embryonic fibroblasts.

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that controls various cellular processes. Protein phosphatase 6 (PP6) is an evolutionarily conserved serine/threonine protein phosphatase with diverse functions in cell signaling. However, it has not been linked to TGF-β signaling. We found that TGF-β treatment increased PP6 protein levels via transcriptional and post-translational regulation. Loss of the Ppp6c gene suppressed TGF-β-induced canonical Smad3 phosphorylation and its transcriptional activity. PP6 knockout also inhibited non-canonical p38 mitogen-activated protein kinase (MAPK) pathway. Moreover, PP6 depletion suppressed cell migration induced by TGF-β. These findings uncovered the role of PP6 as a positive regulator for TGF-β signaling.