scholarly journals Protein phosphatase 2A is expressed in response to colony-stimulating factor 1 in macrophages and is required for cell cycle progression independently of extracellular signal-regulated protein kinase activity

1999 ◽  
Vol 339 (3) ◽  
pp. 517-524 ◽  
Author(s):  
Nicholas J. WILSON ◽  
Suzanne T. MOSS ◽  
Xavier F. CSAR ◽  
Alister C. WARD ◽  
John A. HAMILTON
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
Colony Stimulating Factor ◽  
Cycle Progression ◽  
Extracellular Signal ◽  
Phosphatase 2A ◽  
Stimulating Factor

Colony-stimulating factor 1 (CSF-1) is required for the development of monocytes/macrophages from progenitor cells and for the survival and activation of mature macrophages. The receptor for CSF-1 is the product of the c-fms proto-oncogene, which, on binding ligand, can stimulate a mitogenic response in the appropriate cells. To investigate which genes are regulated in response to CSF-1-stimulation in murine bone-marrow-derived macrophages (BMM), we employed mRNA differential display reverse transcriptase-mediated PCR to identify cDNA species induced by CSF-1. Both Northern and Western blot analyses confirmed the increased expression of one of the cDNA species identified as coding for the catalytic subunit of protein phosphatase 2A (PP2A), an observation not previously reported during the response to a growth factor. To determine the significance of the increased expression of PP2A in response to CSF-1, the PP2A inhibitor okadaic acid (OA) was added to CSF-1-treated BMM and found to inhibit DNA synthesis in a dose-dependent manner. Further analysis with flow cytometry in the presence of OA led to the novel conclusion that PP2A activity is critical for CSF-1-driven BMM cell cycle progression in both early G1 and S phases. Surprisingly, in the light of previous studies with other cells, the PP2A-dependent proliferation could be dissociated from activation by extracellular signal-regulated protein kinase (ERK) in macrophages because OA did not affect either the basal or CSF-1-induced ERK activity in BMM. Two-dimensional SDS/PAGE analysis of lysates of 32P-labelled BMM, which had been treated with CSF-1 in the presence or absence of OA, identified candidate substrates for PP2A.

Identification of a protein phosphatase 2A family member that regulates cell cycle progression in Trypanosoma brucei

2014 ◽  
Vol 194 (1-2) ◽  
pp. 48-52 ◽  
Author(s):  
Karen G. Rothberg ◽  
Neal Jetton ◽  
James G. Hubbard ◽  
Daniel A. Powell ◽  
Vidya Pandarinath ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Family Member ◽  
Trypanosoma Brucei ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
Cycle Progression ◽  
Phosphatase 2A

scholarly journals Signaling from Polyomavirus Middle T and Small T Defines Different Roles for Protein Phosphatase 2A

1998 ◽  
Vol 18 (12) ◽  
pp. 7556-7564 ◽  
Author(s):  
Karen P. Mullane ◽  
Mara Ratnofsky ◽  
Xavier Culleré ◽  
Brian Schaffhausen
Keyword(s):  
Cell Cycle ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
T Antigen ◽  
Functional Difference ◽  
Cycle Progression ◽  
Jun Kinase ◽  
Phosphatase 2A ◽  
Promote Cell Cycle Progression

ABSTRACT Polyomavirus causes a broad spectrum of tumors as the result of the action of its early proteins. This work compares signaling from middle T antigen (MT), the major transforming protein, to that from small T antigen (ST). The abilities of MT mutants to promote cell cycle progression in serum-starved NIH 3T3 cells were compared. Transformation-defective mutants lacking association with SHC or with phosphatidylinositol 3-kinase (PI3-K) retained the ability to induce DNA synthesis as measured by bromodeoxyuridine incorporation. Only when both interactions were lost in the Y250F/Y315F double mutant was MT inactive. ST promoted cell cycle progression in a manner dependent on its binding of protein phosphatase 2A (PP2A). Since the Y250F/Y315F MT mutant was wild type for PP2A binding yet unable to promote cell cycle progression, while ST was capable of promoting cell cycle progression, these experiments revealed a functional difference in MT and ST signaling via PP2A. Assays testing the abilities of MT and ST to induce the c-fos promoter and to activate c-jun kinase led to the same conclusion. ST, but not Y250F/Y315F MT, was able to activate the c-fos promoter through its interaction with PP2A. In contrast, MT, but not ST, was able to activate c-jun kinase by virtue of its interaction with PP2A.

scholarly journals Regulation of the Cell Cycle by Protein Phosphatase 2A in Saccharomyces cerevisiae

2006 ◽  
Vol 70 (2) ◽  
pp. 440-449 ◽  
Author(s):  
Yu Jiang
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Phosphatase 2A ◽  
Direct Target ◽  
Cycle Regulation

SUMMARY Protein phosphatase 2A (PP2A) has long been implicated in cell cycle regulation in many different organisms. In the yeast Saccharomyces cerevisiae, PP2A controls cell cycle progression mainly through modulation of cyclin-dependent kinase (CDK) at the G2/M transition. However, CDK does not appear to be a direct target of PP2A. PP2A affects CDK activity through its roles in checkpoint controls. Inactivation of PP2A downregulates CDK by activating the morphogenesis checkpoint and, consequently, delays mitotic entry. Defects in PP2A also compromise the spindle checkpoint and predispose the cell to an error-prone mitotic exit. In addition, PP2A is involved in controlling the G1/S transition and cytokinesis. These findings suggest that PP2A functions in many stages of the cell cycle and its effect on cell cycle progression is pleiotropic.

scholarly journals Regulation of Mih1/Cdc25 by protein phosphatase 2A and casein kinase 1

2008 ◽  
Vol 180 (5) ◽  
pp. 931-945 ◽  
Author(s):  
Gayatri Pal ◽  
Maria T.Z. Paraz ◽  
Douglas R. Kellogg
Keyword(s):  
Cell Cycle ◽  
Protein Phosphatase ◽  
Feedback Loop ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
Casein Kinase ◽  
Cycle Progression ◽  
Signaling Mechanism ◽  
Casein Kinase 1 ◽  
Phosphatase 2A

The Cdc25 phosphatase promotes entry into mitosis by removing cyclin-dependent kinase 1 (Cdk1) inhibitory phosphorylation. Previous work suggested that Cdc25 is activated by Cdk1 in a positive feedback loop promoting entry into mitosis; however, it has remained unclear how the feedback loop is initiated. To learn more about the mechanisms that regulate entry into mitosis, we have characterized the function and regulation of Mih1, the budding yeast homologue of Cdc25. We found that Mih1 is hyperphosphorylated early in the cell cycle and is dephosphorylated as cells enter mitosis. Casein kinase 1 is responsible for most of the hyperphosphorylation of Mih1, whereas protein phosphatase 2A associated with Cdc55 dephosphorylates Mih1. Cdk1 appears to directly phosphorylate Mih1 and is required for initiation of Mih1 dephosphorylation as cells enter mitosis. Collectively, these observations suggest that Mih1 regulation is achieved by a balance of opposing kinase and phosphatase activities. Because casein kinase 1 is associated with sites of polar growth, it may regulate Mih1 as part of a signaling mechanism that links successful completion of growth-related events to cell cycle progression.

Colony-stimulating factor-1 (CSF-1) receptor-mediated macrophage differentiation in myeloid cells: a role for tyrosine 559-dependent protein phosphatase 2A (PP2A) activity

2001 ◽  
Vol 358 (2) ◽  
pp. 431-436 ◽  
Author(s):  
Kerrie-Ann McMAHON ◽  
Nicholas J. WILSON ◽  
Denese C. MARKS ◽  
Tina L. BEECROFT ◽  
Genevieve A. WHITTY ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Myeloid Cells ◽  
Differentiation Process ◽  
Colony Stimulating Factor ◽  
Macrophage Differentiation ◽  
Pp2a Activity ◽  
Dependent Signal ◽  
Phosphatase 2A ◽  
Stimulating Factor

M1 myeloid cells transfected with the wild-type (WT) colony-stimulating factor-1 (CSF-1) receptor (CSF-1R; M1/WT cells) undergo CSF-1-dependent macrophage differentiation. By mutation studies, we have provided prior evidence that tyrosine 559 in the CSF-1R cytoplasmic domain governs the Src-dependent differentiation pathway. Further components of this pathway were then sought. We report that the extent of CSF-1-mediated tyrosine phosphorylation of protein phosphatase 2A (PP2A), and the associated loss of its activity were reduced in M1 cells transfected with the CSF-1R with a tyrosine-to-phenylalanine mutation at position 559 (M1/559 cells), compared with the corresponding responses in CSF-1-treated M1/WT cells. This evidence for an involvement of a reduction in PP2A activity in the differentiation process was supported by the restoration of the defect in the CSF-1-mediated differentiation of M1/559 cells by the addition of the PP2A inhibitor, okadaic acid. It was also found that the degree of activation of extracellular-signal-regulated kinase (ERK) activities by CSF-1 was reduced in M1/559 cells, suggesting their involvement in the differentiation process. These data suggest that PP2A and ERK form part of the Src-dependent signal-transduction cascade governing CSF-1-mediated macrophage differentiation in M1 cells.

scholarly journals Differential methylation and altered conformation of cytoplasmic and nuclear forms of protein phosphatase 2A during cell cycle progression.

1995 ◽  
Vol 129 (2) ◽  
pp. 397-410 ◽  
Author(s):  
P Turowski ◽  
A Fernandez ◽  
B Favre ◽  
N J Lamb ◽  
B A Hemmings
Keyword(s):  
Cell Cycle ◽  
Conformational Changes ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
Differential Methylation ◽  
Control Mechanisms ◽  
The Core ◽  
Phosphatase 2A ◽  
G1 Cells

Protein phosphatase 2A (PP2A) appears to be involved in the regulation of many cellular processes. Control mechanisms that lead to the activation (and deactivation) of the various holoenzymes to initiate appropriate dephosphorylation events remain obscure. The core components of all PP2A holoenzymes are the catalytic (PP2Ac) and 63-65-kD regulatory (PR65) subunits. Monospecific and affinity-purified antibodies against both PP2Ac and PR65 show that these proteins are ubiquitously localized in the cytoplasm and the nucleus in nontransformed fibroblasts. As determined by quantitative immunofluorescence the core subunits of PP2A are twofold more concentrated in the nucleus than in the cytoplasm. Detailed analysis of synchronized cells reveals striking changes in the nuclear to cytoplasmic ratio of PP2Ac-specific immunoreactivity albeit the total amounts of neither PP2Ac nor PR65 in each compartment alters significantly during the cell cycle. Our results imply that differential methylation of PP2Ac occurs at the G0/G1 and G1/S boundaries. Specifically a demethylated form of PP2Ac is found in the cytoplasm of G1 cells, and in the nucleus of S and G2 cells. In addition nuclear PP2A holoenzymes appear to undergo conformational changes at the G0/G1 and G1/S boundaries. During mitosis PP2A is lost from the nuclear compartment, and unlike protein phosphatase 1 shows no specific association with the condensed chromatin.

Sign in / Sign up

Export Citation Format

Share Document