Saccharomyces cerevisiae Homologs of Mammalian B and B′ Subunits of Protein Phosphatase 2A Direct the Enzyme to Distinct Cellular Functions

Abstract

Protein phosphatase 2A (PP2A) is a major cellular serine/threonine protein phosphatase, present in the cell in a variety of heterotrimeric forms that differ in their associated regulatory B-subunit. Cloning of the mammalian B subunit has allowed the identification of a highly homologous Saccharomyces cerevisiae gene, RTS1. Disruption of the gene results in a temperaturesensitive growth defect that can be suppressed by expression of rabbit B ␣ or B ␥ isoforms. The B ␣ subunit is much more effective in restoring normal growth at 37°C than B ␥. Immunoprecipitated Rts1p was found associated with type 2A-specific protein phosphatase activity that is sensitive to 2 nM okadaic acid, but not to 100 nM phosphatase inhibitor-2, and to be phosphorylated in vivo. However, overexpression of RTS1 was unable to suppress the cold sensitivity, defective cytokinesis, and abnormal cell morphology resulting from defects in the CDC55 gene, which encodes the yeast homolog of a different B subunit of another form of 2A phosphatase, PP2A 1 . These results indicate that Rts1p is a yeast homolog of the mammalian B subunit and that the various regulatory B-subunits of PP2A are not functionally redundant but direct the enzyme to distinct cellular functions.

Cyclin G2 is a centrosome-associated nucleocytoplasmic shuttling protein that influences microtubule stability and induces a p53-dependent cell cycle arrest

“…Deletion mutants of RTS1 in S. cerevisiae, or its homologs in S. pombe, exhibit spindle orientation and septation defects [35]. Moreover, overexpression of mammalian B' subunits in S. cerevisiae results in abnormal elongated cellular morphology [27]. Finally, PP2A B' subunits are localized to and bundle planar MT webs in Drosophila, and are required for planar cell polarity, in both and fly and zebrafish [69].…”

“…The various regulatory B-type subunits direct PP2A to distinct subcellular localizations and modulate its substrate specificity [24][25][26][27]. A role for PP2A in regulation of cytoskeletal associated activities is suggested by the observations that a portion of total PP2A/C is localized to microtubules (MTs), intermediate filaments and centrosomes [24,26,28].…”

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

“…These phosphatases consist of heteromeric protein complexes . The PP2A holoenzyme contains one of the two redundant catalytic subunits (PP2Ac), Pph21, Pph22 (Sneddon et al 1990;Ronne et al 1991), a scaffolding subunit, Tpd3 (van Zyl et al 1992), and one of the two regulatory subunits, Cdc55 or Rts1 (Healy et al 1991;Zhao et al 1997). The PP2A-related phosphatase is mainly found as a complex between the catalytic subunit, Sit4 (Arndt et al 1989), and one of the four regulatory subunits, Sap4, Sap155, Sap185 and Sap190 (Luke et al 1996).…”

Vimentin Dephosphorylation by Protein Phosphatase 2A Is Modulated by the Targeting Subunit B55

“…By analogy to PP1, in which associated noncatalytic subunits target the catalytic subunit to different subcellular compartments and/or substrates, it was proposed that the B-type regulators act as targeting subunits for PP2A (Hubbard and Cohen, 1993). Indeed, B subunits affect the substrate specificity of PP2A in vitro and in vivo (Agostinis et al, 1987;Cegielska et al, 1994;Kamibayashi et al, 1994;Zhao et al, 1997). Distinct subcellular localization has been reported for some B subunits (McCright et al, 1996;Tehrani et al, 1996).…”