The 55 kd regulatory subunit of Drosophila protein phosphatase 2A is required for anaphase

Mayer-Jaekel, Regina E.; Ohkura, Hiroyuki; Sunkel, Cláudio E.; Baumgärtner, Stefan; Hemmings, Brian A.; Glover, David M.

doi:10.1016/0092-8674(93)90080-a

Cited by 220 publications

(182 citation statements)

References 52 publications

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“…Its cytoplasmic localization is consistent with the absence of a nuclear localization signal in the primary structure of B55 isoforms (Mayer et al, 1991;Zolnierowicz et al, 1994). Moreover, all processes in which B55-containing PP2A holoenzymes have been implicated to date appear to be cytoplasmic (Healy et al, 1991;Mayer-Jaekel et al, 1993, 1994Uemura et al, 1993;Lee et al, 1994;Pitcher et al, 1995;Hansra et al, 1996;Sontag et al, 1996). In contrast, members of the B56 and B72 families of regulatory subunits might mediate nuclear functions of PP2A (Hendrix et al, 1993a;McCright et al, 1996).…”

mentioning

confidence: 71%

“…Our results using OA (Figure 1) and the immunolocalization of B55 using Ab55 recomb prompted us to analyze vimentin distribution in Hs68 cells lacking B55. Because B55-containing PP2A holoenzymes were reported to be involved during mitotic progression (Mayer-Jaekel et al, 1993), when both cellular morphology and vimentin distribution are highly modified (Chou et al, 1990), we used only cells in interphase. For this Hs68 fibroblasts were made quiescent by serum deprivation and microinjected 2-3 h after being refed, allowing analysis for 22-24 h before cells entered mitosis (Girard et al, 1992).…”

Section: Molecular Biology Of the Cell 2006mentioning

confidence: 99%

“…Our observations that B55/PP2A modulates vimentin phosphorylation might be a key in understanding how mutant alleles of B55 can lead to developmental defects in Drosophila (Uemura et al, 1993;Shiomi et al, 1994). Such a role in modulating IF dynamics may also explain the effects of mutant B55 alleles on mitotic transit in yeast and Drosophila (Healy et al, 1991;Mayer-Jaekel et al, 1993;Wang and Burke, 1997), in which IF proteins, such as vimentin and lamins, undergo significant, phosphorylation-induced reorganization.…”

Section: Role Of If Dephosphorylation By Pp2amentioning

confidence: 99%

“…The lack of functional B55 in yeast and Drosophila causes severe aberrations in mitotic transit (Healy et al, 1991;Mayer-Jaekel et al, 1993;Wang and Burke, 1997) presumably because of the lack of dephosphorylation of certain p34 cdc2 phosphorylated sites (Ferrigno et al, 1993;. It was recently also reported that B55 associates with the microtubule network (Sontag et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…The 55-kDa regulatory subunit B55 (or PR55) was one of the first B-type regulators to be identified in skeletal muscle preparations of PP2A, and subsequent cDNA cloning revealed evolutionary conservation from yeast to human (Healy et al, 1991;Mayer et al, 1991;Pallas et al, 1992;Mayer-Jaekel et al, 1993). The lack of functional B55 in yeast and Drosophila causes severe aberrations in mitotic transit (Healy et al, 1991;Mayer-Jaekel et al, 1993;Wang and Burke, 1997) presumably because of the lack of dephosphorylation of certain p34 cdc2 phosphorylated sites (Ferrigno et al, 1993;. It was recently also reported that B55 associates with the microtubule network (Sontag et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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

Turowski

Myles

Hemmings

et al. 1999

MBoC

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101

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The intermediate filament protein vimentin is a major phosphoprotein in mammalian fibroblasts, and reversible phosphorylation plays a key role in its dynamic rearrangement. Selective inhibition of type 2A but not type 1 protein phosphatases led to hyperphosphorylation and concomitant disassembly of vimentin, characterized by a collapse into bundles around the nucleus. We have analyzed the potential role of one of the major protein phosphatase 2A (PP2A) regulatory subunits, B55, in vimentin dephosphorylation. In mammalian fibroblasts, B55 protein was distributed ubiquitously throughout the cytoplasm with a fraction associated to vimentin. Specific depletion of B55 in living cells by antisense B55 RNA was accompanied by disassembly and increased phosphorylation of vimentin, as when type 2A phosphatases were inhibited using okadaic acid. The presence of B55 was a prerequisite for PP2A to efficiently dephosphorylate vimentin in vitro or to induce filament reassembly in situ. Both biochemical fractionation and immunofluorescence analysis of detergent-extracted cells revealed that fractions of PP2Ac, PR65, and B55 were tightly associated with vimentin. Furthermore, vimentinassociated PP2A catalytic subunit was displaced in B55-depleted cells. Taken together these data show that, in mammalian fibroblasts, the intermediate filament protein vimentin is dephosphorylated by PP2A, an event targeted by B55. INTRODUCTIONProtein phosphatase 2A (PP2A) is implicated in a significant array of cellular processes, including metabolism, DNA replication, transcription, translation, cell cycle progression, and membrane-to-nuclear signal transduction (for review, see Shenolikar, 1994;Wera and Hemmings, 1995). Regulatory flexibility is conferred by the association of a constant dimeric core of a 36-kDa catalytic (PP2Ac) and a 65-kDa (PR65 or A) subunit with a third, variable B subunit . To date three families of B subunits have been identified, which we will refer to as B55, B56, and B72, according to the predicted molecular weight of their founding member (Mayer et al., 1991;Hendrix et al., 1993a;McCright and Virshup, 1995). At least 10 individual genes code for B-type regulators, with this number being further increased by the additional presence of alternatively spliced forms of certain messages (Hendrix et al., 1993a;Csortos et al., 1996;McCright et al., 1996;Tanabe et al., 1996;Tehrani et al., 1996;Zolnierowicz et al., 1996). 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). The 55-kDa regulatory subunit B55 (or PR55) was one of the first B-type re...

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mentioning

confidence: 71%

Section: Molecular Biology Of the Cell 2006mentioning

confidence: 99%

Section: Role Of If Dephosphorylation By Pp2amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Turowski

Myles

Hemmings

et al. 1999

MBoC

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101

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CtCdc55p and CtHal3p: Two putative regulatory proteins from Candida tropicalis with long acidic domains

Rodriguez

Ali

Serrano

1996

Yeast

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Inhibition of mouse egg chromosome decondensation due to meiotic apparatus derangement induced by the protein phosphatase inhibitor, okadaic acid

Moses

1996

J. Exp. Zool.

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The transition from metaphase to interphase involves protein dephosphorylation. Genetic and immunologic evidence suggest that protein phosphatase (PP) 1 and PP 2A may be required for this transition. Okadaic acid, a specific inhibitor of PP 1 and 2A, prevents the exit from metaphase in mammalian cells, but also disrupts the mitotic apparatus. Since disruption of the spindle itself causes cell cycle arrest, the present study was carried out to determine whether okadaic acid‐treated cells fail to exit from metaphase because PP 1 and/or 2A activity is required, or because of spindle disruption. It was possible to distinguish between these two alternatives by including the protein kinase inhibitor, 6‐dimethylaminopurine (6‐DMAP), in the culture medium, since cells treated with 6‐DMAP exit from metaphase despite disruption of the spindle. Mouse eggs, physiologically arrested at metaphase of the second meiotic division, complete meiosis and enter interphase when exposed to the calcium ionophore A23187. When eggs were exposed to 80 or 100 nM okadaic acid for 8 h, the meiotic spindle disappeared and the chromosomes disjoined. Nuclei did not form in eggs treated with okadaic acid and A23187, but did form in eggs treated with okadaic acid, A23187, and 6‐DMAP. Therefore, eggs treated with okadaic acid have the capacity to exit from metaphase and enter interphase. © 1996 Wiley‐Liss, Inc.

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The 55 kd regulatory subunit of Drosophila protein phosphatase 2A is required for anaphase

Cited by 220 publications

References 52 publications

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

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

CtCdc55p and CtHal3p: Two putative regulatory proteins from Candida tropicalis with long acidic domains

Inhibition of mouse egg chromosome decondensation due to meiotic apparatus derangement induced by the protein phosphatase inhibitor, okadaic acid

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