Abstract
Serine/threonine phosphatases achieve substrate diversity by forming distinct holoenzyme complexes in cells. Although the PPP family of serine/threonine phosphatase family members such as PP1 and PP2A are well known to assemble and function as holoenzymes, none of the PPM family members were so far shown to act as holoenzymes. Here, we provide evidence that PPM1G, a member of PPM family of serine/threonine phosphatases, forms a distinct holoenzyme complex with the PP2A regulatory subunit B56δ. B56δ promotes the re-localization of PPM1G to the cytoplasm where the phosphatase can access a discrete set of substrates. Further, we unveil α-catenin, a component of adherens junction, as a new substrate for the PPM1G-B56 phosphatase complex in the cytoplasm. B56δ-PPM1G dephosphorylates α-catenin at serine 641, which is necessary for the appropriate assembly of adherens junctions and the prevention of aberrant cell migration. Collectively, we reveal a new holoenzyme with PPM1G-B56δ as integral components, in which the regulatory subunit provides accessibility to distinct substrates for the phosphatase by defining its cellular localization.