Global assessment of its network dynamics reveals that the kinase Plk1 inhibits the phosphatase PP6 to promote Aurora A activity

Science Signaling
Arminja N KettenbachScott A Gerber

Abstract

Polo-like kinase 1 (Plk1) is an essential protein kinase that promotes faithful mitotic progression in eukaryotes. The subcellular localization and substrate interactions of Plk1 are tightly controlled and require its binding to phosphorylated residues. To identify phosphorylation-dependent interactions within the Plk1 network in human mitotic cells, we performed quantitative proteomics on HeLa cells cultured with kinase inhibitors or expressing a Plk1 mutant that was deficient in phosphorylation-dependent substrate binding. We found that many interactions were abolished upon kinase inhibition; however, a subset was protected from phosphatase opposition or was unopposed, resulting in persistent interaction of the substrate with Plk1. This subset includes phosphoprotein phosphatase 6 (PP6), whose activity toward Aurora kinase A (Aurora A) was inhibited by Plk1. Our data suggest that this Plk1-PP6 interaction generates a feedback loop that coordinates and reinforces the activities of Plk1 and Aurora A during mitotic entry and is terminated by the degradation of Plk1 during mitotic exit. Thus, we have identified a mechanism for the previously puzzling observation of the Plk1-dependent regulation of Aurora A.

References

Mar 13, 1986·Biochemical and Biophysical Research Communications·T TamaokiF Tomita
Sep 19, 2002·The Journal of Biological Chemistry·Young-Joo JangRaymond L Erikson
Apr 18, 2003·Current Biology : CB·Patrick A EyersJames L Maller
Aug 27, 2003·The Journal of Cell Biology·Rüdiger NeefFrancis A Barr
Sep 4, 2003·Genome Research·Li LiDavid S Roos
Dec 19, 2003·Nucleic Acids Research·M A HarrisUNKNOWN Gene Ontology Consortium
Dec 19, 2003·Nucleic Acids Research·Evelyn CamonRolf Apweiler
Jan 22, 2004·The Journal of Cell Biology·Catherine Lindon, Jonathon Pines
Feb 12, 2004·Bioinformatics·M J L de HoonS Miyano
Jun 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·David L SatinoverDavid L Brautigan
Jun 3, 2004·Nature Reviews. Molecular Cell Biology·Francis A BarrErich A Nigg
Jun 8, 2004·Bioinformatics·Alok J Saldanha
Jun 26, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Geoffrey I Shapiro
Jan 29, 2005·The EMBO Journal·Christian PreisingerFrancis A Barr
Dec 31, 2005·Nucleic Acids Research·Feng ChenDavid S Roos
Feb 8, 2006·Current Biology : CB·Rüdiger NeefFrancis A Barr
Feb 13, 2007·Current Biology : CB·Martin SteegmaierWolfgang J Rettig
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mark G ManfrediChristopher F Claiborne
Jun 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert W WilkinsonStephen Green
Jan 12, 2008·Biochemistry·Bjarki StefanssonDavid L Brautigan
May 15, 2008·Developmental Cell·Mark PetronczkiJan-Michael Peters
Jul 11, 2008·Nature·Libor MacůrekRené H Medema
Oct 30, 2008·Nucleic Acids Research·Daniel BarrellRolf Apweiler
Mar 24, 2009·Nature Reviews. Molecular Cell Biology·Vincent Archambault, David M Glover
May 7, 2010·The Journal of Biological Chemistry·Robert D Van HornXiang S Ye
Sep 24, 2010·Molecular & Cellular Proteomics : MCP·Anna SantamariaErich A Nigg
Dec 7, 2010·Nature Methods·Hyungwon ChoiAlexey I Nesvizhskii
Mar 17, 2011·The Biochemical Journal·Hoi Tang Ma, Randy Y C Poon
May 20, 2011·Nature·Björn SchwanhäusserMatthias Selbach

❮ Previous
Next ❯

Citations

Feb 10, 2019·Biomolecules·Margarida Moura, Carlos Conde
Dec 25, 2019·The Journal of Cell Biology·Elizabeth M ParkAndrew J Holland
Sep 29, 2019·Cellular and Molecular Life Sciences : CMLS·Giulia Bertolin, Marc Tramier
May 14, 2020·The Journal of Cell Biology·Therese M GerbichAmy S Gladfelter
Jun 6, 2020·Essays in Biochemistry·Dimitriya H Garvanska, Jakob Nilsson
Jun 25, 2020·Cells·Cecilia Aquino PerezLibor Macurek
Nov 18, 2018·The Journal of Cell Biology·Jakob Nilsson
Aug 16, 2018·Science Signaling·Vladimir Joukov, Arcangela De Nicolo
Aug 27, 2021·Scientific Data·Deborah O Dele-OniJacob D Jaffe

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.