SACCHAROMYCES-CEREVISIAE HOMOLOGS OF MAMMALIAN B-SUBUNIT AND B'-SUBUNITS OF PROTEIN PHOSPHATASE-2A DIRECT THE ENZYME TO DISTINCT CELLULAR FUNCTIONS

Protein phosphatase 2A (PP2A) is a major cellular serine/threonine pro tein phosphatase, present in the cell in a variety of heterotrimeric f orms that differ in their associated regulatory B-subunit. Cloning of the mammalian B' subunit has allowed the identification of a highly ho mologous Saccharomyces cerevisiae gene, RTS1. Disruption of the gene r esults in a temperature-sensitive growth defect that can be suppressed by expression of rabbit B'alpha or B'gamma isoforms. The B'alpha subu nit is much more effective in restoring normal growth at 37 degrees C than B'gamma. Immunoprecipitated Rts1p was found associated with type 2A-specific protein phosphatase activity that is sensitive to 2 nM oka daic acid, but not to 100 nM phosphatase inhibitor-2, and to be phosph orylated in vivo. However, overexpression of RTS1 was unable to suppre ss the cold sensitivity, defective cytokinesis, and abnormal cell morp hology resulting from defects in the CDC55 gene, which encodes the yea st 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 PP2 A are not functionally redundant but direct the enzyme to distinct cel lular functions.