B23/Nucleophosmin Serine 4 Phosphorylation Mediates Mitotic Functions of Polo-like Kinase 1

Zhang, Hong; Shi, Xianglin; Paddon, Harry B.; Hampong, Maggie; Dai, Wei; Pelech, Steven

doi:10.1074/jbc.m403264200

Cited by 77 publications

(78 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because PLK1 controls progression of cells from G2 to M, we next analyzed the expression of PLK1 by immunoblotting as well as the activity of PLK1 by measuring the phosphorylation of nucleophosmin at serine 4, a direct PLK1 substrate (33) (Fig. 8A).…”

Section: Resultsmentioning

confidence: 99%

G Protein-coupled Receptor Kinase 5 Is Localized to Centrosomes and Regulates Cell Cycle Progression

Michal

Beeharry

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: G protein-coupled receptor kinases (GRKs) are important regulators of receptor function although little is known about their cellular localization. Results: GRK5 is localized in the centrosome during interphase and regulates normal cell cycle progression. Conclusion: GRKs appear to dynamically modulate regulation of the cell cycle. Significance: These findings reveal an additional mechanism by which plasma membrane signaling can regulate the cell cycle.

show abstract

Section: Resultsmentioning

confidence: 99%

G Protein-coupled Receptor Kinase 5 Is Localized to Centrosomes and Regulates Cell Cycle Progression

Michal

Beeharry

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Another study by Zhang et al [48] revealed that a mitosis-specific phosphorylation event occurs in NPM at a conserved Ser-4 residue by Plk1. Interfering with Ser-4 phosphorylation of NPM in HeLa cells by the overexpression of a NPM mutant carrying point mutations at this phosphorylation site leads to abnormalities in centrosome duplication, centrosome segregation, and cytokinesis.…”

Section: Npm Phosphorylationmentioning

confidence: 99%

Nucleophosmin and human cancer

Lim

Wang

2006

Cancer Detection and Prevention

105

100

View full text Add to dashboard Cite

Nucleophosmin (NPM) is a nucleolar phosphoprotein that shuttles between the nucleus and cytoplasm during the cell cycle. NPM has several interacting partners and diverse cellular functions, including the processing of ribosomal RNA, centrosome duplication and the control of cellular processes to ensure genomic stability. Subcellular localization of NPM appears to be strongly correlated with NPM functions and cell proliferation. NPM is phosphorylated mainly at its central acidic domain by several upstream kinases, and its phosphorylation appears to be involved in regulating its functions in ribosome biogenesis and centrosome duplication. Recent studies suggest that NPM may act as a licensing factor to maintain proper centrosome duplication and that the Ran/ CRM1 nucleocytoplasmic complex regulates local trafficking of NPM to centrosomes by interacting through its nuclear export sequence (NES) motif. Here, we provide a brief overview of NPM functions and its roles in human carcinogenesis, and discuss our recent findings related to the potential mechanisms underlying its regulation of centrosome duplication.

show abstract

“…e Reported in vivo Plk1 site (41). f Reported in vivo Plk1 site (42). g Reported in vivo Plk1 site (43).…”

Section: Figmentioning

confidence: 99%

Combination of Chemical Genetics and Phosphoproteomics for Kinase Signaling Analysis Enables Confident Identification of Cellular Downstream Targets

Oppermann¹,

Grundner-Culemann²,

Kumar³

et al. 2012

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Delineation of phosphorylation-based signaling networks requires reliable data about the underlying cellular kinasesubstrate interactions. We report a chemical genetics and quantitative phosphoproteomics approach that encompasses cellular kinase activation in combination with comparative replicate mass spectrometry analyses of cells expressing either inhibitor-sensitive or resistant kinase variant. We applied this workflow to Plk1 (Polo-like kinase 1) in mitotic cells and induced cellular Plk1 activity by wash-out of the bulky kinase inhibitor 3-MB-PP1, which targets a mutant kinase version with an enlarged catalytic pocket while not interfering with wild-type Plk1. We quantified more than 20,000 distinct phosphorylation sites by SILAC, approximately half of which were measured in at least two independent experiments in cells expressing mutant and wild-type Plk1. Based on replicate phosphorylation site quantifications in both mutant and wild-type Plk1 cells, our chemical genetic proteomics concept enabled stringent comparative statistics by significance analysis of microarrays, which unveiled more than 350 cellular downstream targets of Plk1 validated by full concordance of both statistical and experimental data. Our data point to hitherto poorly characterized aspects in Plk1-controlled mitotic progression and provide a largely extended resource for functional studies. We anticipate the described strategies to be of general utility for systematic and confident identification of cellular protein kinase substrates. Molecular & Cellular Proteomics 11: 10.1074/mcp.O111.012351, 1-12, 2012.Reversible protein phosphorylation by protein kinases represents a key control mechanism in signal transmission and controls nearly all aspects of cellular physiology. Quantitative proteomics approaches that incorporate techniques such as stable isotope labeling by amino acids in cell culture (SILAC), 1 phosphopeptide fractionation and enrichment by strong cation exchange (SCX), and ion metal affinity chromatography (IMAC) together with sensitive high resolution MS analysis and automated peptide identification and quantification have made it possible to monitor phosphorylation-based signaling on a global scale (1-4). Because signaling networks are defined by the underlying kinase-substrate relationships, systematic approaches are required for the comprehensive and confident assignment of cellular kinase substrates (5). To identify cellular substrates, the catalytic activity of a kinase of interest needs to be rapidly regulated to capture a high fraction of direct phosphorylation events. This implies that protein kinase ablation by genetic knockout or RNA interference can be of limited utility, because of secondary changes that can accumulate during the time required for cellular kinase depletion (3, 5). In contrast, pharmacological interference by small molecules allows for rapid modulation of kinase activity and should therefore enable unbiased monitoring of signaling perturbations when combined with advanced MS-based proteomics. S...

show abstract

B23/Nucleophosmin Serine 4 Phosphorylation Mediates Mitotic Functions of Polo-like Kinase 1

Cited by 77 publications

References 50 publications

G Protein-coupled Receptor Kinase 5 Is Localized to Centrosomes and Regulates Cell Cycle Progression

G Protein-coupled Receptor Kinase 5 Is Localized to Centrosomes and Regulates Cell Cycle Progression

Nucleophosmin and human cancer

Combination of Chemical Genetics and Phosphoproteomics for Kinase Signaling Analysis Enables Confident Identification of Cellular Downstream Targets

Contact Info

Product

Resources

About