DIFFERENTIAL SUBCELLULAR-LOCALIZATION OF PROTEIN-PHOSPHATASE-1-ALPHA,PROTEIN-PHOSPHATASE-1-GAMMA-1, AND PROTEIN-PHOSPHATASE-1-DELTA ISOFORMS DURING BOTH INTERPHASE AND MITOSIS IN MAMMALIAN-CELLS

Protein phosphatase-1 (PP-1) is involved in the regulation of numerous metabolic processes in mammalian cells. The major isoforms of PP-1, a lpha, gamma 1, and delta, have nearly identical catalytic domains, but they vary in sequence at their extreme NH2 and COOH termini. With spe cific antibodies raised against the unique COOH-terminal sequence of e ach isoform, we find that the three PP-1 isoforms are each expressed i n all mammalian cells tested, but that they localize within these cell s in a strikingly distinct and characteristic manner. Each isoform is present both within the cytoplasm and in the nucleus during interphase , Within the nucleus, PP-1 alpha associates with the nuclear matrix, P P-1 gamma 1 concentrates in nucleoli in association with RNA, and PP-1 delta localizes to nonnucleolar whole chromatin. During mitosis, PP-1 alpha is localized to the centrosome, PP-1 gamma 1 is associated with microtubules of the mitotic spindle, and PP-1 delta strongly associat es with chromosomes. We conclude that PP-1 isoforms are targeted to st rikingly distinct and independent sites in the cell, permitting unique and independent roles for each of the isoforms in regulating discrete cellular processes.