The Interconversion of Protein Phosphatase 2A between PP2A1and PP2A0during Retinoic Acid-Induced Granulocytic Differentiation and a Modification on the Catalytic Subunit in S Phase of HL-60 Cells

Zhu, Tang; Matsuzawa, Shu‐ichi; Mizuno, Yusuke; Kamibayashi, Craig; Mumby, Marc C.; Andjelković, Nataša; Hemmings, Brian A.; Onoé, Kazunori; Kikuchi, Kunimi

doi:10.1006/abbi.1996.9835

Cited by 36 publications

(29 citation statements)

References 45 publications

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“…The fetal versus adult difference in methylation status also predicted that fetal liver would contain more PP2A in the heterotrimeric form relative to the heterodimeric form, which was indeed the case. Contradictory data have been published with regard to the effect of catalytic subunit methylation on catalytic activity, with one group observing a moderate increase in phosphatase activity [41], another seeing no direct effect [42], and a third demonstrating decreased activity [43]. Our results showed that in liver methylation status correlates with higher phosphatase specific activity, although this effect can not be separated from the effect of methylation in promoting formation of the heterotrimeric complex.…”

Section: Discussioncontrasting

confidence: 38%

Subunit composition and developmental regulation of hepatic protein phosphatase 2A (PP2A)

Yoo¹,

Boylan²,

Brautigan³

et al. 2007

Archives of Biochemistry and Biophysics

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The prototypical form of the Ser/Thr phosphatase PP2A is a heterotrimeric complex consisting of catalytic subunit (C), A and B regulatory subunits. C-terminal methylation of PP2A-C influences holoenzyme assembly. Using late gestation development in the rat as an in vivo model of liver growth, we found that PP2A-C protein and activity levels were higher in fetal compared to adult liver extracts. However, unmethylated PP2A-C was much higher in the adult extracts. In MonoQ fractionation, unmethylated C eluted separately from methylated C, which was present predominantly in ABC heterotrimers. Gel filtration chromatography revealed that some unmethylated C was present as free catalytic subunit. In addition, a significant proportion of PP2A was in inactive forms that may involve novel regulatory subunits. Our results indicate that methylation of PP2A-C appears to be a primary determinant for the biogenesis of PP2A heterotrimers.

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Section: Discussioncontrasting

confidence: 38%

Subunit composition and developmental regulation of hepatic protein phosphatase 2A (PP2A)

Yoo¹,

Boylan²,

Brautigan³

et al. 2007

Archives of Biochemistry and Biophysics

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“…These findings indicate that the B subunit content of the heterotrimeric enzyme may be subject to cell cycle control. In another example, the composition of PP2A heterotrimers was transiently altered during the initial stage of retinoic acid-induced granulocytic differentiation (45).…”

Section: Discussionmentioning

confidence: 99%

The Scaffolding A/Tpd3 Subunit and High Phosphatase Activity Are Dispensable for Cdc55 Function in the Saccharomyces cerevisiae Spindle Checkpoint and in Cytokinesis

Koren¹,

Rainis²,

Kleinberger

2004

Journal of Biological Chemistry

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Protein serine/threonine phosphatase 2A (PP2A) is a multifunctional enzyme whose trimeric form consists of a scaffolding A subunit, a catalytic C subunit, and one of several regulatory B subunits (B, B , and B؆). The adenovirus E4orf4 protein associates with PP2A by directly binding the B or B subunits. An interaction with an active PP2A containing the B subunit, or its homologue in yeast, Cdc55, is required for E4orf4-induced apoptosis in mammalian cells and for induction of growth arrest in Saccharomyces cerevisiae. In this work, Cdc55 was randomly mutagenized by low-fidelity PCR amplification, and Cdc55 mutants that lost the ability to transduce the E4orf4 toxic signal in yeast were selected. The mutations obtained by this protocol inhibited the association of Cdc55 with E4orf4, or with the PP2A-AC subunits, or both. Functional analysis revealed that a mutant that does not bind Tpd3, the yeast A subunit, as well as wild type Cdc55 in a tpd3⌬ background, can form a heterodimer with the catalytic subunit. This association requires C subunit carboxyl methylation. The residual phosphatase activity associated with Cdc55 in the absence of Tpd3 is sufficient to maintain a partially active spindle checkpoint and to prevent cytokinesis defects.PP2A 1 is one of the major protein serine/threonine phosphatases in the cell, which plays a role in several cellular processes, including metabolism, transcription, RNA splicing, translation, cell cycle progression, morphogenesis, signal transduction, development, and transformation (1, 2).Several reports indicate that the predominant form of PP2A in cells is a heterotrimer consisting of three subunits. Two of them, the 36-kDa catalytic C subunit and the 63-kDa scaffolding A subunit (PR65), form the core enzyme, and the regulatory B subunit binds the core enzyme to form the holoenzyme. The A and C subunits both exist as two isoforms (␣ and ␤), which are closely related, whereas the B subunit is variable, and its multiple isoforms belong to at least three unrelated gene families, B/B55/PR55 (␣-␦ isoforms), BЈ/B56/PR61 (␣-⑀ isoforms), and BЉ/PR72/PR130/PR59/PR48 (3). The core PP2A enzyme has also been shown to bind other cellular proteins, including striatin and SG2NA (4). Viral proteins, such as the SV40 small t antigen and the polyomavirus small and middle T antigens, can replace the cellular B subunits (5). The various cellular PP2A B subunits target the PP2A holoenzyme to different substrates and dictate its subcellular localization (reviewed in Ref.3).In Saccharomyces cerevisiae, two closely related genes, PPH21 and PPH22, redundantly encode the major PP2A catalytic subunit (6). TPD3 encodes the only A subunit, and two distinct B subunits, encoded by CDC55 and RTS1, are highly homologous to mammalian B and BЈ, respectively (7-9). Mutations of CDC55 are viable, but yield defects in cytokinesis and in the spindle checkpoint and result in abnormal cell morphology. Methylation of the C-terminal leucine residue of the PP2A catalytic subunit by a specific methyltransferase increase...

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“…263,264 The differential effect of TGFb on monocytic versus granulocytic differentiation may be explained by the enhancement of Smad2/3 phosphorylation and nuclear translocation during vitamin D3-induced monocytic differentiation, and the reduction of Smad2/3 phosphorylation and nuclear accumulation during ATRA-induced granulocytic differentiation. [265][266][267] Conclusions/future perspectives Emerging evidence indicates that multiple signaling pathways are activated during cytokine-induced myeloid differentiation and that these pathways may play critical roles in facilitating the differentiation process. Moreover, the impact that activation of a given pathway has on normal myeloid differentiation may be markedly different from the impact that is seen when that pathway is activated in a differentiation-defective leukemia.…”

Section: Pi3k-akt Pathwaymentioning

confidence: 99%

Signal transduction pathways that contribute to myeloid differentiation

Miranda

Johnson

2007

Leukemia

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The production of mature, differentiated myeloid cells is regulated by the action of hematopoietic cytokines on progenitor cells in the bone marrow. Cytokines drive the process of myeloid differentiation by binding to specific cell-surface receptors in a stage-and lineage-specific manner. Following the binding of a cytokine to its cognate receptor, intracellular signal-transduction pathways become activated that facilitate the myeloid differentiation process. These intracellular signaling pathways may promote myelopoiesis by stimulating expansion of a progenitor pool, supporting cellular survival during the differentiation process, or by directly driving the phenotypic changes associated with differentiation. Ultimately, pathways that drive the differentiation process converge on myeloid transcription factors, including PU.1 and the C/EBP family, that are critical for differentiation to proceed. While much is known about the cytokines, cytokine receptors and transcription factors that regulate myeloid differentiation, less is known about the precise roles that specific signaling mediators play in promoting myeloid differentiation. Recently, however, the application of novel pharmacologic inhibitors, siRNA strategies, and transgenic and knockout models has begun to shed light on the involvement and function of signaling pathways in normal myeloid differentiation. This review will discuss the roles that key signaling pathways and mediators play in myeloid differentiation.

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The Interconversion of Protein Phosphatase 2A between PP2A1and PP2A0during Retinoic Acid-Induced Granulocytic Differentiation and a Modification on the Catalytic Subunit in S Phase of HL-60 Cells

Cited by 36 publications

References 45 publications

Subunit composition and developmental regulation of hepatic protein phosphatase 2A (PP2A)

Subunit composition and developmental regulation of hepatic protein phosphatase 2A (PP2A)

The Scaffolding A/Tpd3 Subunit and High Phosphatase Activity Are Dispensable for Cdc55 Function in the Saccharomyces cerevisiae Spindle Checkpoint and in Cytokinesis

Signal transduction pathways that contribute to myeloid differentiation

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