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

Transforming growth factor-beta (TGF-ß) 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-ß signaling. We found that TGF-ß treatment increased PP6 protein levels via transcriptional and post-translational regulation. Loss of the Ppp6c gene suppressed TGF-ß-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-ß. These findings uncovered the role of PP6 as a positive regulator for TGF-ß signaling.