Zds1/Zds2-PP2ACdc55 complex specifies signaling output from Rho1 GTPase

Acknowledgments We thank David Pellman, John Pringle, Daniel Lew, Masaki Mizunuma, Kenji Irie, and the Yeast Genome Resource Center for yeast strains and plasmids and members of Yoshida Laboratory and Keiko Kono for their support. Multicopy suppressor screening for gef∆ was initiated in the Pellman Laboratory with the help of Didem Ilter. This research was supported by Sprout grant from Brandeis University (E.M. Jonasson and S. Yoshida), an American-Italian Cancer Foundation Postdoctoral fellowship (V. Rossio), and a Massachusetts Life Sciences Center grant (S. Yoshida).Peer reviewedPublisher PD

Spatial regulation of Cdc55–PP2A by Zds1/Zds2 controls mitotic entry and mitotic exit in budding yeast

Zds1/2 regulate mitotic progression by directing the nucleocytoplasmic distribution of Cdc55–PP2A

Zds2p Regulates Swe1p-dependent Polarized Cell Growth in Saccharomyces cerevisiae via a Novel Cdc55p Interaction Domain

A C-terminal region in Zds2p (ZH4) is required for regulation of Swe1p-dependent polarized cell growth and this region is necessary and sufficient for interaction with protein phosphatase 2A regulatory subunit, Cdc55p. Our results indicate that the Zds proteins regulate the Swe1p-dependent G2/M checkpoint in a CDC55-dependent manner

Greatwall promotes cell transformation by hyperactivating AKT in human malignancies

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Protein Kinase C Controls Binding of Igo/ENSA Proteins to Protein Phosphatase 2A in Budding Yeast

Protein phosphatase 2A (PP2A) plays important roles in controlling mitosis in all eukaryotic cells. The form of PP2A that controls mitosis is associated with a conserved regulatory subunit that is called B55 in vertebrates and Cdc55 in budding yeast. The activity of this form of PP2A can be inhibited by binding of conserved Igo/ENSA proteins. Although the mechanisms that activate Igo/ENSA to bind and inhibit PP2A are well understood, little is known about how Igo/Ensa are inactivated. Here, we have analyzed regulation of Igo/ENSA in the context of a checkpoint pathway that links mitotic entry to membrane growth in budding yeast. Protein kinase C (Pkc1) relays signals in the pathway by activating PP2A(Cdc55). We discovered that constitutively active Pkc1 can drive cells through a mitotic checkpoint arrest, which suggests that Pkc1-dependent activation of PP2A(Cdc55) plays a critical role in checkpoint signaling. We therefore used mass spectrometry to determine how Pkc1 modifies the PP2A(Cdc55) complex. This revealed that Pkc1 induces changes in the phosphorylation of multiple subunits of the complex, as well as dissociation of Igo/ENSA. Pkc1 directly phosphorylates Cdc55 and Igo/ENSA, and phosphorylation site mapping and mutagenesis indicate that phosphorylation of Cdc55 contributes to Igo/ENSA dissociation. Association of Igo2 with PP2A(Cdc55) is regulated during the cell cycle, yet mutation of Pkc1-dependent phosphorylation sites on Cdc55 and Igo2 did not cause defects in mitotic progression. Together, the data suggest that Pkc1 controls PP2A(Cdc55) by multiple overlapping mechanisms