Differential subcellular localization of protein phosphatase-1 alpha, gamma1, and 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, alpha, gamma1, and delta, have nearly identical catalytic domains, but they vary in sequence at their extreme NH2 and COOH termini. With specific antibodies raised against the unique COOH-terminal sequence of each isoform, we find that the three PP-1 isoforms are each expressed in all mammalian cells tested, but that they localize within these cells 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, PP-1 gamma1 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 gamma1 is associated with microtubules of the mitotic spindle, and PP-1 delta strongly associates with chromosomes. We conclude that PP-1 isoforms are targeted to strikingly distinct and independent sites in the cell, permitting unique and independent roles for each of the isoforms in regulating discrete cellular processes.
Andreassen
P R
PR
Institut de Biologie Structurale Jean-Pierre Ebel (CEA-CNRS), 38027 Grenoble cedex 1, France.
Lacroix
F B
FB
Villa-Moruzzi
E
E
Margolis
R L
RL
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D007527:Isoenzymes / Q000032:analysis* / Q000276:immunology; D008938:Mitosis; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000032:analysis* / Q000276:immunology; D054645:Protein Phosphatase 1; D013347:Subcellular Fractions
D007527:Isoenzymes; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1